Next Article in Journal
Solvent Vapour Detection with Cholesteric Liquid Crystals—Optical and Mass-Sensitive Evaluation of the Sensor Mechanism
Previous Article in Journal
Novel Feature Modelling the Prediction and Detection of sEMG Muscle Fatigue towards an Automated Wearable System
Previous Article in Special Issue
One-Dimensional Oxide Nanostructures as Gas-Sensing Materials: Review and Issues
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:

A Comprehensive Review of Glucose Biosensors Based on Nanostructured Metal-Oxides

Department of Advanced Technology Fusion, Konkuk University, Seoul 143-701, Korea
KFnSC Center, Konkuk University, Seoul 143-701, Korea
Korea Research Institute of Standard and Science, Yuseong, Daejeon 305-340, Korea
Department of Applied Chemistry, Konkuk University, Chungju 380-701, Korea
Author to whom correspondence should be addressed.
Sensors 2010, 10(5), 4855-4886;
Received: 11 March 2010 / Revised: 7 April 2010 / Accepted: 15 April 2010 / Published: 12 May 2010
(This article belongs to the Special Issue Metal-Oxide Based Nanosensors)


Nanotechnology has opened new and exhilarating opportunities for exploring glucose biosensing applications of the newly prepared nanostructured materials. Nanostructured metal-oxides have been extensively explored to develop biosensors with high sensitivity, fast response times, and stability for the determination of glucose by electrochemical oxidation. This article concentrates mainly on the development of different nanostructured metal-oxide [such as ZnO, Cu(I)/(II) oxides, MnO2, TiO2, CeO2, SiO2, ZrO2, and other metal-oxides] based glucose biosensors. Additionally, we devote our attention to the operating principles (i.e., potentiometric, amperometric, impedimetric and conductometric) of these nanostructured metal-oxide based glucose sensors. Finally, this review concludes with a personal prospective and some challenges of these nanoscaled sensors.

1. Introduction

Diabetes mellitus is one of the principal causes of death and disability in the World, and is highly responsible for heart disease, kidney failure, and blindness. About 200 million people in the world are afflicted with diabetes mellitus. This figure is expected to rise up to more than three hundred million by 2030 [1]. Frequent testing of physiological blood glucose levels to avoid diabetic emergencies, is crucial for the confirmation of effective treatment [25]. Therefore, the development of high sensitive, low-cost, reliable glucose sensors having an excellent selectivity has been the subject of concern for decades, not only in medical science but also in the food industries [6,7]. Glucose oxidase (GOx)-based glucose biosensors have prevalently had a hold on the glucose sensor research and development over the last four decades and the market place as well. This is due to the high demand of sensitive and reliable blood glucose monitoring in biological and clinical aspects [811]. There are still some disadvantages of enzyme-based glucose determination. Examples include complicated enzyme immobilization, critical operating conditions such as optimum temperature and pH, chemical instability, and high cost [12,13].
The historical commencement of biosensors was in 1960s with the pioneering work of Clark and Lyons [14], and the first enzyme-based glucose sensor commenced by Updike and Hicks in 1967 [15]. Since then, an extensive research have been done on the amperometric, potentiometric, and impedimetric or conductometric glucose biosensors based on the GOx [1623], that catalyzes the oxidation of glucose to produce gluconic acid as shown in equation (1):
D glucose + O 2 + H 2 O GOx D gluconic acid + H 2 O 2
The activity of enzymes is obviously affected by the temperature, pH, humidity, and toxic chemicals [24]. To solve these problems, many enzyme-free sensors have been investigated to improve the electrocatalytic activity and selectivity toward the oxidation of glucose. This can be done by using: (1) inert metals such as Pt [2527], Au [2830] and Ni [31,32]; (2) metal alloys containing Pt, Au, Pb, Ir, Ru, Cu, and Pd [2,3337]; and (3) metal-dispersed carbon nanotubes (CNTs) framework in which Pt, Pb, Pd, or Au are mixed with CNTs to form nanocomposites [3842]. However, these materials are unsatisfactory with regards to sensitivity and selectivity, are high costing, and show quick loss of activity by adsorption and accumulation of intermediates or chloride ions [2,43]. Therefore, the development of highly selective, sensitive, inexpensive, reliable and fast enzymatic/nonenzymatic glucose sensor is still imperatively needed.
In recent years, an increasing number of researchers have explored the production of novel nano-scale metal oxides, noble metal-doped metal oxides, metal oxide-CNTs nanocomposites, and metal oxide-polymer composites. Novel analytical devices based on nanostructured metal oxides are cost-effective, highly sensitive due to the large surface-to-volume ratio of the nanostructure, and additionally show excellent selectivity when coupled to biorecognition molecules with simple design [4447]. Some metal oxides such as ZnO and CeO2 show high isoelectric point (IEP), excellent biocompatibility, and easy synthetic procedure for nanostructure that enables reliable immobilization of GOx. On the other hand, MnO2 and ZrO2 having low IEP values are suitable for the immobilization of high IEP proteins. The catalytic ability of transition metal oxides such as CuO and NiO of nonenzymatic direct electrooxidation of glucose is one of the attractive properties in glucose detection allowing minimum fabrication cost and stable glucose sensors. This article provides a comprehensive review of the state-of-the-art research activities that focus on several important metal-oxide nanostructures and nanocomposites in addition to the application of nanostructured metal oxides to glucose sensing. Also, the most commonly-used electrochemical detection methods for the glucose sensing will be discussed.

2. Electrochemical Principles of Glucose Biosensors

There is no doubt that the development of an ideal glucose sensor must be top issue for the biosensor industry. Numerous processes and methodologies have been developed for creating new glucose biosensors such as electrochemical methods [48], colorimetry [49], conductometry [50], optical methods [51], and fluorescent spectroscopy [52]. Among them, the electrochemical glucose sensors have attracted the most attention over the last 40 years because of their unbeaten sensitivity and selectivity. Additionally, electrochemical techniques show lower detection limit, faster response time, better long term stability and inexpensiveness. The extremely sensitive fluorescent spectroscopy can even detect a single molecule and a few fluorescence-based in vivo monitoring of glucose are available, but none of them are practically applicable to diabetes management [53]. The electrochemical glucose sensors are basically categorized into three major groups depending on the measurement principles: i.e., potentiometric, amperometric, impedemetric or conductometric sensors.

2.1. Potentiometric Glucose Sensor

Potentiometry is commonly used to measure glucose concentrations greater than 10−5 M, which is in the physiological range in most cases. The potential difference between the reference electrode and the indicator electrode is measured at zero current flow. The ideally nonpolarizable reference electrode provides a constant potential, while the indicator electrode shows an erratic potential depending on the concentration of the analytes. The zero current potentials applied between those two electrodes are recorded as a function of the concentrations of target analytes in a logarithmic manner [48]. The potential difference at the electrode-electrolyte interface arising from unbalanced activities of species i in the electrolyte phase (s) and in the electrode phase (β) is related by the following Nernst equation:
E = E o + RT Z i F   ln   a i s a i β
where E0 is the standard electrode potential, R the gas constant, T the absolute temperature, F the faraday constant, ai the activity of species i, and Zi the number of moles of electron involved.
Potentiometric sensors are divided into the metal-oxide sensitive field effect transistor (MOSFET), the light-addressable potentiometric sensor (LAPS), the ion-sensitive field effect transistors (ISFET) and the ion-selective electrodes (ISE). Ali et al. developed a commercial MOSFET using a GOx modified ZnO nanowire. GOx-functionalized ZnO nanowires were grown on the Ag wire and then directly connected to the MOSFET gate (Figure 1) [54]. They tested the response time and the stability of the MOSFET sensor by using three different GOx/ZnO modified Ag electrodes, i.e., vertically aligned, uniform nonaligned, and nonuniform nonaligned ZnO nanowires. The results showed that well aligned ZnO-modified electrode displayed a good stability, short response time (<100 ms), and improved detection limit. They also further demonstrated that the GOx/ZnO modified MOSFET is able to be used for the immobilization of other biomolecules to make versatile electrodes for biosensing.
ISFETs and LAPS have attracted much attention for biosensing application being especially convenient for construction. The principles of LAPS are based on the activation of semiconductor by a light emitting diode [55]. Seki et al. developed a LAPS based on SiO2/Al2O3 film grown on an n-type Si substrate. The GOx was immobilized on the film at various pH in the range of 3 to 11. Upon exposure to the light emitting diode, the equilibrium potential of the GOx-modified SiO2/Al2O3 film was increased linearly with the increase of glucose concentration up to 4 mM. An increased sensitivity was also observed by introducing hexacyanoferrate (III) as an alternative to oxygen because the reduced form of flavin adenine dinucleotide (FADH2) positioned within the active site of the GOx is more easily oxidized with hexacyanoferrate (III) [56]. While, the principle of ISFET is based on the local potential generated by surface ions from a solution [55]. Luo et al. built up a glucose sensitive enzymatic field effect transistor (ENFET) by modifying the gate surface of the ISFET with SiO2 nanoparticles and GOx. The SnO2 based glucose sensor showed a good stability and reproducibility with a detection limit of ca. 0.025 mM [57]. A few reports are available on nonenzymetic potentiometric glucose sensor based on poly(aniline boronic acid) suggested by Shoji and Freund [58,59]. These sensors showed improved sensitivity for fructose compared to glucose.

2.2. Amperometric Glucose Sensor

Amperometry is a quite sensitive electrochemical technique in which the signal of interest is current that is linearly dependent on the target concentration by applying a constant bias potential. Glucose is oxidized at the working electrode composed of a noble metal formed by either the physical vapor deposition or screen-printing and the biorecognition species such as GOx for glucose sensing [60]. An amperometric biosensor comprises two or three electrodes. The former consists of a reference and a working electrode. Application of the two-electrode system to biosensors is limited, because at high current flow the potential control becomes difficult as a result of sizable IR drop. Instead, the third electrode is commonly introduced as an auxiliary counter electrode having a large surface area to make most of current flows between the counter and the working electrodes, though voltage is still applied between the working and the reference electrodes.
There are three modes of the glucose oxidation referred to as the first, the second and the third generation glucose sensors depending on the electron transfer mechanisms. The nanostructured metal-oxide based glucose sensor belong to the third generation. Figure 2(A) depicts the first generation glucose sensor where oxygen is used as a mediator between the electrode and the GOx. The oxygen is reduced to form hydrogen peroxide in the presence of glucose by flavin adenine dinucleotide (FAD), a prosthetic group of GOx, and FADH2 redox couple. The reduction rate of the oxygen is proportional to the glucose concentration that is quantified by either measuring the augmentation of hydrogen peroxide or decrement of the oxygen concentration [5,61]. On the other hand, artificial electron mediators (M), e.g., ferro/ferricyanide, hydroquinone, ferrocene, and various redox organic dyes between the electrode and the GOx are employed in the second generation glucose sensor. These mediators make the electron transfer rate between the electrode and the GOx faster and also give a way of getting around for a case when limited oxygen pressure commonly observed from the first generation glucose sensor [62,63]. Figure 2(B) represents the second generation glucose sensor, where Mox and Mred are the oxidized and reduced forms of mediator, respectively. The reduced form of flavin group (FADH2) of GOx is reoxidized in presence of glucose by the reduction of Mox to form Mred. The output current signal generated, when further oxidation of Mred occurs at the electrode surface, is proportional to the glucose concentration [5,62,63].
In the third generation glucose sensor, the GOx is directly coupled to the electrode. The direct electron transfer efficiently generates an amperometric output signal. The improved sensing performance by the direct electron transfer has been realized by incorporating the enzyme with metal nanoparticles [64,65], and semiconductive nanomaterials [66,67]. The nanocrystalline metal-oxide plays a vital role in the enzyme immobilization owing to its highly specific surface area, good biocompatibility and stability [68]. Liu et al. fabricated a novel third generation amperometric glucose sensor based on the aligned ZnO nanorod formed on an ITO electrode (Figure 3). The immobilized GOx on the ZnO nanorod shows still high catalytic activity, effective protection by Nafion (perfluorosulfonate ionomer) membrane cast on the film, a wide linear range with good selectivity and freedom from the interference effects of uric acid and ascorbic acid in real samples [69].
In recent years progressive attempts have been made to determine the glucose without any enzyme for the reliable fast determination [7072]. Most enzymeless electrochemical glucose sensors rely on the properties of the electrode materials, on which the glucose is oxidized directly. Carbon, platinum, gold and nanostructured CuO-modified CNTs have been widely investigated as candidates for improving the sensing performance of enzymeless sensors [73,74]. However, some problems including poor selectivity and low sensitivity due to the surface poisoning by the adsorbed intermediates or chloride ions still remain [75].

2.3. Impedimetric/Conductometric Glucose Sensor

The impedimetric biosensor is less frequently used as compared to the potentiometric and the amperometric ones. Electrochemical impedance spectroscopy (EIS) is a powerful analytical tool which allows us to effectively visualize the actual electrical double layer structure of a modified electrode [76] although recording of an impedance spectrum within a broad frequency range is time consuming. The glucose does not affect the dielectric spectrum in the MHz frequency region [77,78] and direct detection of the glucose is available. The expression of impedance in a simple RC circuit is as follows:
Z 2 = R 2 + 1 ( 2 f C ) 2
where Z is impedance, R the resistance and C the capacitance.
Conductance is the reciprocal of resistance, so sometimes the impedimetric biosensor is also called a conductometric biosensor [78]. Shervedani et al. developed a quantitative method for the determination of glucose based on the EIS measurements. In this method, the GOx was immobilized on the mercaptopropionic acid (MPA) self-assembled monolayer (SAM) modified gold electrode. Parabenzoquinone (PBQ) was used as an electron mediator which is reduced to hydroquinone (H2Q). The EIS measurements showed that the charge transfer resistance (Rct) decreases with the increase of the glucose concentration due to the increase of the diffusion current density by the H2Q oxidation. The nondestructive and straightforward method showed a dynamic range of glucose determination with linear variation of the sensor response (1/Rct) as a function of glucose concentration in a solution [79]. Recently, versatile biosensing materials such as semiconducting CNTs and conducting polymers have been introduced [80]. Besteman et al. combined the GOx to the sidewall of the single-wall carbon nanotube (SWNT) by the use of a cross linker and found conductance decrease of the SWNT as well as the change of capacitance. The conductance increased upon exposure to glucose indicating that an enzyme-based single molecular level biosensor is available by the use of the SWNT [78]. Very few reports are available on nanostructured metal-oxide modified glucose sensor based on the conductometry or the EIS [81]. Ansari et al. covalently immobilized GOx on the SnO2 nanostructured thin film grown on anodized aluminum oxide (AAO) pores by the plasma enhanced chemical vapor deposition (PECVD) leading to the conductivity increase of the film. This film showed higher sensitivity towards glucose as compare to other simple nanostrucutres [82]. More improved sensitivity and wider linear response range could be available by tailoring the material properties, for example active surface area, three-dimensional structure, and electrical conductance of the film.

3. Glucose Sensor Based on Metal-Oxides

Metal-oxide based sensors are very sensitive, relatively inexpensive and have the advantage of rapid response associated with specific nanostructures such as nanowire, nanorod, nanotube, nanoparticle, nanofibre, CNT modified metal-oxide and so on. In this section, we will discuss recent development of enzymatic or nonenzymatic glucose sensors based on various nanostructured metal-oxides. It should be mentioned that during the last two decades tremendous efforts have been made for the detection of glucose based on nanostructured metal oxides and their composites. In Table 1 we tabulate metal oxides applicable to glucose sensors reported so far and give brief descriptions in terms of the detection methods, availability of enzymatic or nonenzymatic operations, sensitivity, detection limit, response time, and applied potential.

3.1. Zinc Oxide (ZnO) Based Glucose Sensor

ZnO nanomaterials have been studied extensively in optics, optoelectronics, sensors, and actuators owing to their semiconducting, piezoelectric, and pyroelectric properties [83]. ZnO has many attractive properties for the fabrication of the metal-oxide based biosensors, for example good biocompatibility, chemical stability, non-toxicity, electrochemical activity and fast electron transfer rate. Most of all, the ZnO substrate provides the GOx having many acidic protons with a better electrode surface for immobilization because the isoelectric point (IEP) of the ZnO is about 9.5, while that of the GOx is 4.2 [84,85]. Moreover, high surface-to-volume ratio of nanostructured ZnO gives the immobilized GOx a better electrical contact to the electrode [86,87]. Among many nanostrucuted ZnO, the ZnO nanorods have been widely studied for the immobilization of biomolecules [69,88,89]. Wei et al. introduced the ZnO nanorod grown on a gold electrode by hydrothermal decomposition followed by the iimobilization of GOx in phosphate buffer solution at pH 7.4. Negatively charged GOx in a neutral or basic solution is electrostatically immobilized on to the positively charged ZnO nanorod in the same solution by applying an anodic potential. The modified electrode showed a high and reproducible sensitivity in short response time and apparent Michaelis-Menten constant towards glucose oxidation was 2.9 mM [90].
Nanoporous ZnO and ZnO nanotubes have improved surface-to-volume ratios and also show highly sensitivity towards glucose oxidation. The porous ZnO:Co nanocluster having an average particle size of 5 nm showed much higher sensitivity (about 13.3 μA mM−1 cm−2) due to the high specific active sites and electrocatalytic activity of the ZnO:Co nanoclusters as well as strong affinity to the GOx [91]. Yang et al. synthesized porous ZnO nanotube arrays on ITO by two-step electrochemical and chemical processes (Figure 4). The Nafion/GOx/ZnO nanotube arrays on ITO electrode showed good mechanical contact between the ITO substrate and the ZnO nanotubes which leads to the improved sensitivity [83]. Similarly, improved sensitivity with the porous tetragonal pyramid-shaped ZnO nanomaterials and the ZnO nanocomb structure were also reported by other groups [9294].
Physically or chemically tailored ZnO nanowires also lead to the high specific surface area and high IEP for efficient immobilization of concentrated GOx and the nanowire structure effectively mediates the electron transfer of the redox reaction [69]. Liu et al. developed a carbon-coated ZnO (C-ZnO) nanowire arrayed electrode by taking advantage of electrical conductivity and chemical stability of the carbon material and the one dimensional channel structure of ZnO nanowires [92]. The Nafion/GOx/C-ZnO nanowired electrode exhibited a pair of well-defined redox peaks at −0.43 and −0.48 V, resulted from the direct electron transfer between the immobilized GOx and the electrode. By contrast, no peaks were observed from both Nafion/GOx and Nafion/C-ZnO nanowired electrodes. Meanwhile, only very weak peaks are detected with a Nafion/GOx/pristine nanowired electrode. The EIS measurements confirmed the fast electron transfer at the C-ZnO nanowired electrode with charge transfer resistance of Fe[(CN)6]3−/4− was ∼85 Ω, much smaller than that at the pristine nanowired electrode (∼400 Ω). The C-ZnO nanowire could be an inexpensive high-performing alternative to the conventional CNT-modified gold film in biosensor applications.
The nanostructured ZnO shows high sensitivity but very poor stability, because the ZnO nano-structure is easily removed from the electrode surface during functionalization [66,86]. Indeed, improved stability without loss of sensitivity or selectivity is one of the big challenges for glucose monitoring. Extensive efforts have been made to retain the catalytic activity of the immobilized GOx for a long time by using carbon-coated ZnO nanowire [95], functionalized CNTs [96], nanosized CaCO3 film [97], NdPO4 nanoparticle-chitosan composite [98], meldolas Blue mediated screen-printed electrodes [99] and many other materials. Wang et al. prepared ZnO nanoparticles and coated them onto a multiwall carbon nanotube (MWNT)-modified electrode for the GOx immobilization to improve the stability. A cationic polydiallyldimethylammonium chloride (PDDA) layer was further coated on the GOx-contained ZnO layer to prevent enzyme leakage [100]. The PDDA/GOx/ZnO/MWNTs film provided the sensing electrode with enhanced sensitivity, lower detection limit and long term stability more than 160 days. Results obtained from this glucose sensor were compared with one hundred human blood serum samples and agreed with the results of conventional spectrometric assay (correlation coefficient, 0.997).
In recent years, monitoring of intracellular glucose levels has received considerable attention and various methods including electrochemical detection [101], use of hypodermic needles [102], and microdialysis [103] have been proposed for the assessment of glucose in interstitial spaces as an alternative site rather than the bloodstream. Recently, Asif et al. developed a functionalized ZnO-nanorod based electrochemical sensor for the selective detection of glucose in human adipocytes and frog oocytes [104]. Hexagonal ZnO nanorods grown on the tip of a silver-covered borosilicate glass capillary make it possible to microinject specific reagents, which can interrupt or activate signal transmission to glucose, into relatively large adipocytes and oocytes. The prepared nanosensor exhibited a glucose-dependent electrochemical potential difference over the concentration range of 0.5–1000 μM versus a micro-sized Ag/AgCl reference electrode with a fast response time (<1 s). Intracellular and extracellular measurements of glucose showed good sensitivity and selectivity without interferences even though the nanosensor encountered stability problems.
Even if ZnO nanomaterials are highly promising electrode materials for glucose sensing, a relatively high potential is still required for operation meaning that unwanted output signal caused by the oxidation of interfering agents such as ascorbic acid (AA) or uric acid (UA), might be usually coexisted with glucose signal in real samples.

3.2. Copper Oxide (CuO/Cu2O) Based Glucose Sensor

Transition metal oxides and alloys significantly enhance direct oxidation of glucose compared with other metals that attribute to the catalytic effect resulting from the multi-electron oxidation mediated by surface metal oxide layers [105,106]. Transition metals such as Cu and Ni can oxidize carbohydrate easily without surface poisoning. Unlike Cu and Ni, corresponding oxides or hydroxides are relatively stable in air and solutions [107,108]. Natural abundance of copper oxide as well as its low production cost, good electrochemical and catalytic properties make the copper oxide to be one of the best materials for electrical, optical and photovoltaic devices, heterogeneous catalysis, magnetic storage media, gas sensing, field-emission emitters, lithium ion electrode and so forth [109111].
Recent advances in nanoscience and nanotechnology have revealed the catalytic effect of copper oxide in relation to nonenzymetic glucose oxidation, voltammetric sensing of carbohydrates and hydrogen peroxide detection with ultra-sensitive response and good stability [112]. Wang et al. prepared Pd (IV)-doped CuO nanofibers (PCNFs) and CuO nanofibers via electrospinning on glassy carbon electrodes (GCE) and investigated the amperometric direct responses to glucose [113]. The PCNFs modified electrode showed excellent selectivity, reproducibility and stability. The Pd in the PCNFs, with lower electron occupancy in 3d orbital compared to the Cu, act as a Lewis acid for adsorption of polar glucose molecule a Lewis bases, via nucleophilic attack by non-bonded electron pairs. The longer resident time for the reactant species within the electrode-electrolyte interface, the more enhanced electrocatalytic activity towards the glucose oxidation [105,114]. A similar approach was also demonstrated by using three-dimensional network of CuO nanofibers (CuO-NFs) and reported improved sensitivity, stability and fast response time compared to the PCNFs modified electrode [115]. The CuO-NFs modified electrode also shows good selectivity and resistance to electrode fouling. Zhuang et al. developed a highly stable and sensitive nonenzymatic glucose sensor based on copper oxide nanowire modified Cu electrode in an alkaline medium [116]. The CuO nanowire can greatly increase the electrocatalytic active area and promote electron transfer rate of glucose oxidation. The CuO modified electrodes could be used repeatedly and were not contaminated with by-product of glucose oxidation. Experimental data for the glucose detection are in good agreement with the results from the spectrophotometric method performed in local hospital in real sample, where interference effect is negligible.
Recently, the existence of CuO nanoparticles as impurities in a CNT-based electrode has been claimed to be responsible for electrocatalytic activity of glucose oxidation [117] as the synthetic procedures of pure CuO nanowire or nanofiber are tedious and time consuming. In addition, air-sensitive copper substrate can make a big sensor-to-sensor variation when exposed to open air under most environmental conditions. Combination of CNTs with copper oxide nanoparticles enhances the electron transfer rate of Cu2O and are successfully applied as an enzyme-free glucose Sensor. Very recently, Zhang et al. and Jiang et al. have developed Cu2O/MWNTs and CuO/MWNTs modified nonenzymatic electrodes for glucose sensing [118,119]. The Cu2O/MWNTs nanocomposites were prepared on GCEs by a new fixure-reduction method at low temperature. It showed higher sensitivity and lower detection limit as compared to the CuO/MWNTs that attributes to the stability factor of those two different copper oxide films [120]. Very few reports are available on CuO based enzymatic glucose sensors for example, immobilization of CuO-GOx mixture within a carbon paste matrix [121] and immobilization of GOx on flower-shaped CuO nanostructured electrode [122].

3.3. Manganese Dioxide (MnO2) Based Glucose Sensor

Most enzymatic glucose sensors take advantage of the reducing power of hydrogen peroxide produced by the degradation of glucose via the GOx involved catalytic reaction. The oxidation of hydrogen peroxide is accompanied by the application of a bias potential at which, however, coexisting species such as AA are also electroactive [123]. Basically, two options are available to avoid the electrochemical activity of interfering agents. One is to employ a permselective membrane and the other one is to lower the applied potential by using electron mediators [124129]. The permselective membrane may decrease the sensitivity and may not completely exclude the interfering effect. As an example of the permselective membrane, MnO2 a strong oxidant has been tested to get rid of interference signals in glucose sensing by Choi et al. [130]. The IEP of MnO2 is quite low (4–5) at pH ranging from 2.8 to 4.5 but at higher pH, MnO2 showed favorable environment for the immobilization of biomolecules [131,132].
Turkusic et al. developed an amperometric glucose sensor based on carbon paste electrodes modified with MnO2 and GOx that operated at pH 9.5 [133]. They also demonstrated glucose degradation mechanism on the MnO2/GOx modified screen printed electrode (SPE) based on heterogeneous carbon material, as shown in Figure 5. The two enzymatic oxidation products, gluconolactone and H2O2 were produced by applying 0.48 V vs. Ag/AgCl. The H2O2 further reacts chemically with MnO2 to produce manganese species having lower oxidation states, which can be electrochemically reoxidized to form MnO2 and the oxidative current flow is directly proportional to the glucose concentration. This rapid electrochemical process is accompanied by a kinetically slower chemical reoxidation of MnO/Mn2O3 coupled with chemical oxidation of H2O2. The MnO2/GOx modified SPE showed partially decreased interfering signals, along with good reproducibility and long term stability.
Poly(diallyldimethylammonium), PDDA/MnO2 and chitosan/MnO2 nanocomposites are excellent electrode materials to minimize interference effect of UA and AA at low potential. Xu et al. fabricated a PDDA/MnO2 nanocomposite on graphite electrode surface at pH 7.0 a favorable pH for the GOx immobilization. As-prepared PDDA/MnO2/GOx modified electrode is free from interferants when operated at 0.46 V [134]. They also suggested chitosan film containing MnO2 nanoparticles where the GOx was entrapped to be immobilized into chitosan hydrogel and showed effective suppression of interfering signals of ascorbates [135].
Chen et al. developed a nonenzymatic electrochemical glucose sensor modified with MnO2/MWNTs [136]. The MnO2/MWNTs electrode displayed high electrocatalytic activity towards the glucose oxidation in alkaline solutions at 0.3V and also strongly resisted toward poisoning by chloride ions. In addition, the problematic interference that occurs by the oxidation of common interfering species such as AA, dopamine (DA), and UA was effectively suppressed in real sample analysis compare to the unmodified MWNTs.

3.4. Titanium Dioxide (TiO2) Based Glucose Sensor

TiO2 nanomaterials are basically biocompatible and environmentally-friendly and have been frequently proposed as a prospective interface for the immobilization of biomolecules [137,138], and widely applied in photochemistry [139141] and electrochemistry [142,143]. Moreover, titanium forms coordination bonds with the amine and carboxyl groups of enzymes and maintains the enzyme’s biocatalytic activity. Nanostructured TiO2 also provides the enzyme with better immobilization environment by enlarging the surface area [144,145].
Sol-gel technology has been widely explored in the field of chemical sensors and biosensors. Especially, the low-temperature sol-gel process enables encapsulation of heat sensitive biomolecules such as enzymes, protein molecules and antibodies [146149]. Various sol-gel derived TiO2 films associated with binding molecules or polymer networks for crack-free porous structures have been characterized and applied to biosensing [150155]. Viticoli et al. developed a third generation amperometric glucose sensor based on nanostructured TiO2 on a porous silicon (p-Si) substrate. The Functionalized TiO2 layers were prepared by the metal organic chemical vapor deposition or by the sol-gel technique at various pressures (0.1–4 torr) and temperatures (300 °C to 800 °C) using Ti(IV) isopropoxide as a starting precursor [156]. Enzyme was directly dip-coated on the TiO2 modified p-Si substrate. Results showed a good linear response with a few seconds of response time.
Recently, Bao et al. have hydrothermally synthesized a new slack TiO2 layer having a uniform porous nanostructure by the use of MWNTs template [157]. The TiO2 nanostructure displayed a big hysteresis loop at high pressure. Abrupt increase of adsorption at high pressure in the nitrogen adsorption and desorption isotherms confirms the presence of porous structure. The porous TiO2 nanostructure has a large capacity for enzyme immobilization that was proved by observing a big change in shape of the hysteresis loop and a significant decrease of the specific surface area of the nanostructure. The applied potential was 0.45 V at pH 6.6 under a N2 atmosphere. Although the porous TiO2 nanostructure-modified GCE strongly depends on pH, it operates at low enough potential to eliminate interference signals of UA and AA.
Fluorescence based glucose sensors have appeared in the literature as an alternative way of continuous monitoring of glucose levels. These sensors are highly specific towards analytes but require built-in probes [158]. A number of reports on reagentless optical biosensors using pH-sensitive fluorescent probes are available [159163]. Fluorometric detection of dissolved oxygen is available since the oxygen is able to quench the fluorescent probe. Doong et al. developed a novel optical arrayed TiO2 biosensor for simultaneous detection of anlaytes containing glucose, urea and glutamate in a serum sample [164]. Carboxyseminaphthorhodamine-1-dextran (SNARF-1-dextran), a single-molecule fluorescent probe, was co-immobilized with glucose dehydrogenase on TiO2 by the sol-gel process. The glucose dehydrogenase decomposes glucose to produce proton and the pH decreases. An enhanced sensitivity at basic condition is primarily attributed to the fluorescent characteristics of the carboxy SNARF-1-dextran that gives strong emission intensity at 630 nm. As-prepared TiO2 arrayed optical sensor showed still good sensitivity even after stored at 4 °C for 1 month.

3.5 Cerium Oxide (CeO2) Based Glucose Sensor

Nanostructured CeO2 is an excellent electrode material because it is a nontoxic, chemically inert and electrically conductive material. It also shows large surface area like other nanostructured materials and good biocompatibility [165173]. Additionally, CeO2 can act as electrochemical redox couple that makes it possible to produce a mediatorless glucose sensor. High IEP (∼9.0) and electron-transfer rate constant (18.3 s−1) with a good surface coverage (1.4 × 10−11 mol cm−2) of CeO2 allow easier enzyme immobilization and direct electron transfer between the active sites of the GOx and the electrode surface [174,175].
Saha et al. deposited nanoporous CeO2 thin film on a Pt coated glass plate using pulsed laser deposition (PLD) [176]. GOx was immobilized on to the CeO2 by the electrostatic interaction between the positively charged CeO2 and the negatively charged GOx at pH 7. Prior to the enzyme immobilization the GOx/Pt electrode was pretreated electrochemically at 0.8 V to activate the CeO2 surface and to remove the oxidizable impurities. The resulting GOx/CeO2/Pt electrode showed a linear response to glucose oxidation with low Michaelis-Menten constant (1.01 mM) indicating enhanced enzyme affinity to glucose. The mechanisms available for the glucose oxidation on the electrode are depicted in Figure 6.
Path A describes direct electron transfer between the GOx and the electrode via oxidation and reduction of CeO2 in which the CeO2 is a better electron acceptor than oxygen. This is clearly confirmed by observing no oxidation peak of H2O2 [177], whereas, in path B, the electron generated by the glucose oxidation might be coupled with reduction of molecular oxygen followed by reduction of CeO2 and then finally transferred to the electrode at acidic condition [178]. Sol-gel derived nanostructured CeO2 film on Au electrode is also available for the GOx immobilization and suggested by Ansari et al. [179]. The GOx physically adsorbed on the CeO2/Au electrode showed a linear response in the range of 0.5 g L−1 to 4 g L−1. The detection limit was 12.0 μM with a shelf life of 12 days. Recently, various nanostructured CeO2 such as nanorod, nanocomb, nanocubes, and nanoflower [180,181] have been synthesized. However, no successful reports about glucose detection are available and the potential application of these nanostructures for glucose sensing is of great interest.

3.6. Silicon Dioxide (SiO2) Based Glucose Sensor

Basically, electrode materials should have good electron transport capacity, bioactivities towards target analytes and provide suitable physical or chemical environments for reliable immobilization of biorecognition molecules. Some metal oxides meet those requirements perfectly, but there are still demands for other nanostructured materials including conducting polymers and CNTs to get more enhanced sensitivity and reliability of a glucose sensor. Indeed, composite materials made from two or more nanostructures are another big issue [182184].
Silica based organic and inorganic nanocomposites are attractive electrode materials since they provide biorecognition molecules with a better entrapment environment and more enhanced electrochemical stability [185]. A mesocellular silica–carbon nanocomposite foam (MSCF) was designed for the GOx immobilization by Wu et al. [186]. The uniformly ordered MSCF showed good biocompatibility, favorable conductivity and hydrophilicity. The narrow pore-size distribution was suitable for the immobilization of not only the GOx but also other redox proteins. A fast electron transfer rate (14.0 ± 1.7 s−1) of the GOx modified MSFC allowed direct electrochemistry and showed a good electrochemical sensitivity to glucose with a linear response range of 50 μM to 5.0 mM with a detection limit of 34 μM at an applied potential of −0.4 V. The low potential for operation prohibits unwanted interference signal in real sample by the oxidation of AA and UA.
Recently, extensive researches have been done on the immobilization of GOx by the use of silica nanocomposites such as unprotected Pt nanoclusters mixed with the nanoscale SiO2 particles [187], chitosan/SiO2 nanocomposites attached on the Pt-MWNTs modified electrode [188], TiO2/SiO2 nanocomposite [189], sol–gel silica film on a prussian blue modified electrode [190]. Porous SiO2 nanofiber is also available for the potentiometric biosensor application [191].
Gopalan et al. made a form of silica network on Nafion and subsequently loaded polyaniline grafted MWNTs (MWNTs-g-PANI) on the Nafion–silica nanocomposite for the GOx immobilization [192]. Nafion, silica, MWNTs, and conducting polymers have individually been known as materials for improving the electrocatalytic activity, electron conduction path, sensitivity, and stability of biosensors, respectively [193195]. The Nafion–silica/MWNTs-g-PANI electrode exhibited a linear response to glucose in the range of 1 mM to 10 mM with a correlation coefficient of 0.9972. The sensitivity was 5.01 μA mM−1 with a low response time (∼6 s). Although the entire fabrication procedure is somewhat complicated and requires high fabrication cost, the Nafion–silica/MWNT-g-PANI composite electrode showed excellent sensing performance with negligible interference from AA, UA, and acetaminophen (AP). The recovery test of the Nafion–silica/MWNTs-g-PANI electrode in real sample was evaluated by the standard addition method, with three times addition of standard glucose solution. Experimental showed that reproducible current response (R.S.D) for three measurements were in the range of 2.9−4.1% with the recovery range of 98.0–105.5.

3.7. Zirconium Oxide (ZrO2) Based Glucose Sensor

Nanostructured ZrO2 is another example for the direct electron transfer between metal-oxide layer and the immobilized GOx for glucose sensing. Because the IEP of ZrO2 is of 4.15 [196], it is suitable for the adsorption of high IEP proteins. Therefore, any other nanomaterial, which can drop down the IEP of ZrO2 when it is mixed with ZrO2 is needed for the application of ZrO2-based electrode to glucose sensing since the IEP of glucose is of 4.2 [197]. The first amperometric glucose sensor based on sol-gel derived ZrO2 was reported by Liu et al. [198]. Since then, a numerous efforts have been reported for the development of nano ZrO2 based biosensors [199201]. Yang et al. prepared ZrO2/Pt-PLL (poly-Lysine) and ZrO2/Pt-PVA (polyvinyl alcohol) to modify pyrolytic graphite (PG) electrodes for the GOx immobilization [202]. Didodecyldimethylammonium bromide (DDAB), a synthetic lipid commonly used as a bio-membrane was introduced to stabilize and protect inorganic nanoparticles. The resulting GOx/ZrO2/Pt-PVA electrode showed largest reaction activity towards glucose oxidation in the presence of ferrocenium hexafluorophosphate (FcPF6) as an electron transfer mediator. On the other hand, no enzymatic activity of the immobilized GOx can be observed on ZrO2/DMSO and ZrO2/DDAB film. So, the use of colloidal platinum by replacing DMSO and DDAB plays an important role in transferring electrons between GOx and the electrode.
Table 2 summarizes characteristics of the most frequently-used metal oxides what we have discussed in the section 3.1 to 3.7 in terms of EIP, the availability of enzymatic or nonenzymatic sensors, the compatibility with CNTs, conducting polymers or metal nanoparticles, and the application for other biosensors.

3.8. Other Metal-Oxide Based Glucose Sensors

Plenty other metal oxides such as NiO, SnO2, MgO, IrO2, WO3, PbO2, RhO2, IrOx, V2O5, Fe3O4, and RuOx have been reported and their use, not only for glucose sensing, but also for many other biosensing applications to improve sensing performances attempted [203213]. In this section we will briefly introduce some of those metal-oxide based sensors, including their applications and future prospects.
In recent years, NiO nanomaterials have received considerable attention due to their broad application to battery cathodes, gas sensors, electrochromic films, magnetic materials and catalysts [214,215]. However, there are only few biosensor applications. Li et al. developed a novel amperometric glucose sensor based on NiO hollow nanosphere [203]. The NiO is suitable for electrostatic immobilization of proteins having low IEP because the IEP of NiO is about 10.7. The hollow-sphered NiO was good responsible for high loading of GOx and showed fast electron transfer with a sensitivity of 3.43 μA mM−1 and a detection limit of 47 μM (S/N = 3).
MgO as a ceramic material has been typically applied to water purification, additives in refractory, paint, and superconductors. Various nanostructured magnesium oxides have been reported [216218] but only a few reports are available for biosensor applications [219,205]. Umar et al. first introduced the application of MgO as an electrode material for glucose sensing [205]. Polyhedral nanocages and nanocrystals of MgO were grown on silicon substrates via non-catalytic simple thermal evaporation process or on a gold surface and used as immobilization matrices for GOx. The resulting Au/MgO/GOx/Nafion electrode showed a good stability and sensitivity of 31.6 μA μM−1 cm−2. The response time was less than 5 seconds.
Kotzian et al. reported an amperometric glucose sensor based on rhodium dioxide (RhO2) modified screen printed carbon electrode for the first time [209]. The GOx were mixed with equal amounts of nafion and then transferred to the RhO2 modified SPE. The flow injection analysis of glucose at an operating potential of 0.2 V vs. Ag/AgCl showed an excellent detection limit of 0.2 mg L−1 when the optimized flow rate was 0.4 mL min−1 in a 0.1 M phosphate buffer (pH 7.5) solution and the interference effect was surprisingly reduced because the operational potential was relatively very low.

4. Conclusion: Future Prospective and Challenges

Numerous efforts have been made to devise an ultrasensitive biosensor for monitoring blood glucose without interference from other electroactive species. With the advent of nanotechnology, the regulation of sensing devices at molecular level is possible to some extent. In spite of the impressive success of glucose monitoring by using various nanomaterials, however, there is still asking for continuous and non-invasive glucose sensing from diabetic patients in hospital with a much more reliable and sensitive glucose sensor. Since metal-oxide nanomaterials have basically large surface-to-volume ratio, high IEP values and provide a better surface for GOx immobilization, scientists have paid much attention to these electrode materials in anticipation of more stable, more sensitive but less interfering free glycemic monitoring. Additionally the metal-oxide based nonenzymatic glucose sensor enables cost-effective direct determination of blood glucose level without any electron transfer mediator and there is no loss of sensitivity due to denaturation of protein enzymes in the immobilization or detection procedures.
This review has briefly summarized the most frequently-used electrochemical methods and metal-oxides, including zinc oxide, copper oxides, manganese dioxide, titanium oxides, cerium oxide and silicon dioxide in glucose biosensors. ZnO and CeO2 having high IEP might be the most suitable electrode materials for glucose sensing. Various nanostructured ZnOs have been reported for glucose monitoring and they showed excellent sensitivity and selectivity. Mediatorless glucose sensing is also available with the CeO2. On the other hand, the nanostructured CuO modified electrode is capable of direct electrooxidation of glucose without enzyme immobilization and reduces the costs of the sensor fabrication. Moreover, CuO nanostructure-modified electrode showed highest sensitivity and lower detection limit compare to other metal oxide based glucose sensors and also showed less interference due to the low operating potential. Many other metal-oxides for example nickel and magnesium oxides are also available for glucose sensing. Some metal-oxides are highly sensitive but show poor stability and serious interference effect because of high potential requirement for operation. On the other hand, other metal-oxides operate at low enough potential not to produce interfering signals and stability problem either but their sensitivity is totally unsatisfactory. Nevertheless, glucose sensing based on novel metal-oxide nanomaterials still has many advantages for the glucose detection in terms of miniaturization and development of semi-invasive or finally non-invasive sensing devices especially for the in vivo detection even though it requires more academic and technical studies for commercialization. Indeed, growing research interest of glucose sensors will continue with increasing prevalence of diabetic patients and the theoretical background and the experimental expertise acquired through investigation of metal-oxide nanostructured glucose sensors will be extended to overall biosensor industry.


This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF-2007-211-C00029) and by Seoul R&BD Program (WR090671). It was also partly supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2008-0062166).


  1. Gavin, J.R. The Importance of Monitoring Blood Glucose. In US Endocrine Disease 2007; Touch Briefings: Atlanta, GA, USA, 2007; pp. 1–3. [Google Scholar]
  2. Wang, J.; Thomas, D.F.; Chen, A. Nonenzymatic Electrochemical Glucose Sensor Based on Nanoporous PtPb Networks. Anal. Chem 2008, 80, 997–1004. [Google Scholar]
  3. King, H.; Aubert, R.E.; Herman, W.H. Global Burden of Diabetes. 1995–2025: Prevalence, Numerical Estimates, and Projections. Diabetes Care 1998, 21, 1414–1431. [Google Scholar]
  4. Wild, S.H.; Roglic, G.; Green., A.; Sicree, R.; King, H. Global Prevalence of Diabetes: Estimates for the Year 2000 and Projections for 2030. Diabetes Care 2004, 27, 1047–1053. [Google Scholar]
  5. Wang, J. Electrochemical Glucose Biosensors. Chem. Rev 2008, 108, 814–825. [Google Scholar]
  6. Wilson, G.S.; Gifford, R. Biosensors for Real-Time in vivo Measurements. Biosens. Bioelectron 2005, 20, 2388–2403. [Google Scholar]
  7. Newman, J.D.; Turner, A.P.F. Home Blood Glucose Biosensors: A Commercial Perspective. Biosens. Bioelectron 2005, 20, 2435–2453. [Google Scholar]
  8. Koschinsky, T; Heinemann, L. Sensors for Glucose Monitoring: Technical and Clinical Aspects. Diabetes Metab Res. Rev 2001, 17, 113–123. [Google Scholar]
  9. Oliver, N.S.; Toumazou, C.; Cass, A.E.G.; Johnston, D.G. Glucose Sensors: A Review of Current and Emerging Technology. Diabetic Med 2009, 26, 197–210. [Google Scholar]
  10. Lin, Y.; Lu, F.; Tu, Y.; Ren, Z. Glucose Biosensors Based on Carbon Nanotube Nanoelectrode Ensembles. Nano Lett 2004, 4, 191–195. [Google Scholar]
  11. Rakow, N.A.; Suslick, K.S. A Colorimetric Sensor Array for Odour Visualization. Nature 2000, 406, 710–712. [Google Scholar]
  12. Reitz, E.; Jia, W.; Gentile, M.; Wang, Y.; Lei, Y. CuO Nanospheres Based Nonenzymatic Glucose Sensor. Electroanalysis 2008, 20, 2482–2486. [Google Scholar]
  13. Sachedina, N.; Pickup, J.C. Performance Assessment of The Medtronic-Minimed Continuous Glucose Monitoring System and Its Use for Measurement of Glycaemic Control in Type 1 Diabetes. Diabet. Med 2003, 20, 1012–1015. [Google Scholar]
  14. Clark, L.C.; Lyons, C. Electrode Systems for Continuous Monitoring in Cardiovascular Surgery. Ann. N. Y. Acad. Sci 2006, 102, 29–45. [Google Scholar]
  15. Updike, S.J.; Hicks, G.P. The Enzyme Electrode. Nature 1967, 214, 986–988. [Google Scholar]
  16. Kang, X.H.; Mai, Z.B.; Zou, X.Y.; Cai, P.X.; Mo, J.Y. A Novel Glucose Biosensor Based On Immobilization of Glucose Oxidase in Chitosan on A Glassy Carbon Electrode Modified with Gold-Platinum Alloy Nanoparticles/Multiwall Carbon Nanotubes. Anal. Biochem 2007, 369, 71–79. [Google Scholar]
  17. Shervedani, R.K.; Mehrjardi, A.H.; Zamiri, N. A Novel Method for Glucose Determination Based On Electrochemical Impedance Spectroscopy Using Glucose Oxidase Self-Assembled Biosensor. Bioelectrochemistry 2006, 69, 201–208. [Google Scholar]
  18. Caras, S.D.; Petelenz, D.; Janata, J. pH-Based Enzyme Potentiometric Sensors. Part 2. Glucose-Sensitive Field Effect Transistor. Anal. Chem 1985, 57, 1920–1923. [Google Scholar]
  19. Tang, H.; Chen, J.H.; Yao, S.Z.; Nie, L.H.; Deng, G.H.; Kuang, Y.F. Amperometric Glucose Biosensor Based On Adsorption of Glucose Oxidase at Platinum Nanoparticle-Modified Carbon Nanotube Electrode. Anal. Biochem 2004, 331, 89–97. [Google Scholar]
  20. Wang, S.G.; Zhang, Q.; Wang, R.L.; Yoon, S.F.; Ahn, J.; Yang, D.J. Multi-Walled Carbon Nanotubes for the Immobilization of Enzyme in Glucose Biosensors. Electrochem. Commun 2003, 5, 800–803. [Google Scholar]
  21. Tsai, Y.C.; Li, S.C.; Chen, J.M. Cast Thin Film Biosensor Design Based on a Nafion Backbone, a Multiwalled Carbon Nanotube Conduit, and a Glucose Oxidase Function. Langmuir 2005, 21, 3653–3658. [Google Scholar]
  22. Wang, J. Glucose Biosensors: 40 Years of Advances and Challenges. Electroanalysis 2001, 13, 983–988. [Google Scholar]
  23. Heller, A.; Feldman, B. Electrochemical Glucose Sensors and Their Applications in Diabetes Management. Chem. Rev 2008, 108, 2482–2505. [Google Scholar]
  24. Schijgerl, K.; Hitzmann, B.; Jurgens, H.; Kullick, T.; Ulber, R.; Weigal, B. Challenges in Integrating Biosensors and FIA for On-Line Monitoring and Control. Trends Biotechnol. 1996, 14, 21–23. [Google Scholar]
  25. Proenca, L.; Lopes, M.I.S.; Fonseca, I.; Kokoh, K.B.; Leger, J.-M.; Lamy, C. Electrocatalytic Oxidation of D-sorbitol on Platinum in Acid Medium: Analysis of the Reaction Products. J. Electroanal. Chem 1997, 432, 237–242. [Google Scholar]
  26. Chen, C.-Y.; Tamiya, E.; Ishihara, K.; Kosugi, Y.; Su, Y.-C.; Nakabayashi, N.; Karube, I. A Biocompatible Needle-Type Glucose Sensor Based on Platinum- Electroplated Carbon Electrode. Appl. Biochem.Biotech 1992, 36, 211–226. [Google Scholar]
  27. Chou, C.-H.; Chen, J.-C.; Tai, C.-C.; Sun, I.-W.; Zen, J.-M. A Nonenzymatic Glucose Sensor Using Nanoporous Platinum Electrodes Prepared by Electrochemical Alloying/Dealloying in a Water-Insensitive Zinc Chloride-1-Ethyl-3 Methylimidazolium Chloride Ionic Liquid. Electroanalysis 2008, 20, 771–775. [Google Scholar]
  28. Kurniawan, F.; Tsakova, V.; Mirsky, V.M. Gold Nanoparticles in Nonenzymatic Electrochemical Detection of Sugars. Electroanalysis 2006, 18, 1937–1942. [Google Scholar]
  29. Feng, D.; Wang, F.; Chen, Z. Electrochemical Glucose Sensor Based On One-Step Construction of Gold Nanoparticle–Chitosan Composite film. Sens. Actuat. B-Chem 2009, 138, 539–544. [Google Scholar]
  30. Tominaga, M.; Nagashima, M.; Nishiyama, K.; Taniguchi, I. Surface Poisoning During Electrocatalytic Monosaccharide Oxidation Reactions at Gold Electrodes in Alkaline Medium. Electrochem. Commun 2007, 9, 1892–1898. [Google Scholar]
  31. Liua, Y.; Teng, H.; Hou, H.; You, T. Nonenzymatic Glucose Sensor Based On Renewable Electrospun Ni Nanoparticle-Loaded Carbon Nanofiber Paste Electrode. Biosens. Bioelectron 2009, 24, 3329–3334. [Google Scholar]
  32. Lu, L.-M.; Zhang, L.; Qu, F.-L.; Lu, H.-X.; Zhang, X.-B.; Wu, Z.-S.; Huana, S.-Y.; Wang, Q.-A.; Shen, G.-L; Yu, R.-Q. A Nano-Ni Based Ultrasensitive Nonenzymatic Electrochemical Sensor for Glucose: Enhancing Sensitivity Through a Nanowire Array Strategy. Biosens. Bioelectron 2009, 25, 218–223. [Google Scholar]
  33. Grace, A.N.; Pandian, K. Synthesis of Gold and Platinum Nanoparticles Using Tetraaniline as Reducing and Phase Transfer Agent—A Brief Study and Their Role in the Electrocatalytic Oxidation of Glucose. J. Phys. Chem. Sol 2007, 68, 2278–2285. [Google Scholar]
  34. Holt-Hindle, P.; Nigro, S.; Asmussen, M.; Chen, A. Amperometric Glucose Sensor Based on Platinum–Iridium Nanomaterials. Electrochem. Commun 2008, 10, 1438–1441. [Google Scholar]
  35. Belousov, V.M.; Vasylyev, M.A.; Lyashenko, L.V.; Vilkova, N.Y; Nieuwenhuys, B.E. The Low-Temperature Reduction of Pd-doped Transition Metal Oxide Surfaces with Hydrogen. J. Chem. Eng 2003, 91, 143–150. [Google Scholar]
  36. Xiao, F.; Zhao, F.; Mei, D.; Mo, Z.; Zeng, B. Nonenzymatic Glucose Sensor Based On Ultrasonic-Electrodeposition of Bimetallic PtM (M = Ru, Pd and Au) Nanoparticles on Carbon Nanotubes–Ionic Liquid Composite Film. Biosens. Bioelectron 2009, 24, 3481–3486. [Google Scholar]
  37. Cui, H.-F.; Ye, J.-S.; Liu, X.; Zhang, W.-D.; Sheu, F.-S. Pt–Pb Alloy Nanoparticle/Carbon Nanotube Nanocomposite: A Strong Electrocatalyst for Glucose Oxidation. Nanotechnology 2006, 17, 2334–2339. [Google Scholar]
  38. Meng, L.; Jin, J.; Yang, G.; Lu, T.; Zhang, H.; Cai, C. Nonenzymatic Electrochemical Detection of Glucose Based on Palladium-Single-Walled Carbon Nanotube Hybrid Nanostructures. Anal. Chem 2009, 81, 7271–7280. [Google Scholar]
  39. Zhu, H.; Lu, X.; Li, M.; Shao, Y.; Zhu, Z. Nonenzymatic Glucose Voltammetric Sensor Based On Gold Nanoparticles/Carbon Nanotubes/Ionic Liquid Nanocomposites. Talanta 2009, 79, 1446–1453. [Google Scholar]
  40. Wang, H.; Zhou, C.; Liang, J.; Yu, H.; Peng, F.; Yang, J. High Sensitivity Glucose Biosensor Based on Pt Eelectrodeposition onto Low-density Aligned Carbon Nanotubes. Int. J. Electrochem. Sci 2008, 3, 1258–1267. [Google Scholar]
  41. Wang, H.; Zhou, C.; Liang, J.; Yu, H.; Peng, F. An Enhanced Glucose Biosensor Modified by Pt/sulfonated- MWCNTs with Layer by Layer Technique. Int. J. Electrochem. Sci 2008, 3, 1180–1185. [Google Scholar]
  42. Xie, J.; Wang, S.; Aryasomayajula, L; Varadan, V.K. Platinum Decorated Carbon Nanotubes for Highly Sensitive Amperometric Glucose Sensing. Nanotechnology 2007, 18, 065503–065512. [Google Scholar]
  43. Sun, Y.; Buck, H.; Mallouk, T.E. Combinatorial Discovery of Alloy Electrocatalysts for Amperometric Glucose Sensors. Anal. Chem 2001, 73, 1599–1604. [Google Scholar]
  44. Liu, A. Towards Development of Chemosensors and Biosensors with Metal-Oxide-Based Nanowires or Nanotubes. Biosens. Bioelectron 2008, 24, 167–177. [Google Scholar]
  45. Zhai, T.; Fang, X.; Liao, M.; Xu, X.; Zeng, H.; Yoshio, B.; Golberg, D. A Comprehensive Review of One-Dimensional Metal-Oxide Nanostructure Photodetectors. Sensors 2009, 9, 6504–6529. [Google Scholar]
  46. Huang, J.; Wan, Q. Gas Sensors Based on Semiconducting Metal Oxide One-Dimensional Nanostructures. Sensors 2009, 9, 9903–9924. [Google Scholar]
  47. Ahammad, A.J.S.; Lee, J.-J.; Rahman, M. A. Electrochemical Sensors Based on Carbon Nanotubes. Sensors 2009, 9, 2289–2319. [Google Scholar]
  48. Wang, Y.; Xu, H.; Zhang, J.; Li, G. Electrochemical Sensors for Clinic Analysis. Sensors 2008, 8, 2043–2081. [Google Scholar]
  49. Morikawa, M.; Kimizuka, N.; Yoshihara, M.; Endo, T. New Colorimetric Detection of Glucose by Means of Electron-Accepting Indicators: Ligand Substitution of [Fe(acac)3−n(phen)n]n+ Complexes Triggered by Electron Transfer from Glucose Oxidase. Chem. Eur. J 2002, 8, 5580–5584. [Google Scholar]
  50. Miwa, Y.; Nishizawa, M.; Matsue, T.; Uchida, I. A Conductometric Glucose Sensor Based on a Twin-Microband Electrode Coated with a Polyaniline Thin Film. Bull. Chem. Soc. Jp 1994, 67, 2864–2866. [Google Scholar]
  51. Mansouri, S.; Schultz, J.S. A Miniature Optical Glucose Sensor Based on Affinity Binding. Nature Biotech 1984, 2, 885–890. [Google Scholar]
  52. Pickup, J.C.; Hussain, F.; Evans, N.D.; Rolinski, O.J.; Birch, D.J.S. Fluorescence-Based Glucose Sensors. Biosens. Bioelectron 2005, 20, 2555–2565. [Google Scholar]
  53. Weiss, S. Fluorescence Spectroscopy of Single Molecules. Science 1999, 283, 1676–1683. [Google Scholar]
  54. Ali, S.M.U.; Nur, O.; Willander, M.; Danielsson, B. Glucose Detection with a Commercial MOSFET Using a ZnO Nanowires Extended Gate. IEEE Trans. Nanotechnol 2009, 8, 678–683. [Google Scholar]
  55. Pohanka, M.; SkládaL, P. Electrochemical Biosensors-Principles and Applications. J. Appl. Biomed 2008, 6, 57–64. [Google Scholar]
  56. Seki, A.; Ikeda, S.-I.; Kubo, I.; Karube, I. Biosensors Based on Light-Addressable Potentiometric Sensors for Urea, Penicillin and Glucose. Anal. Chim. Acta 1998, 373, 9–13. [Google Scholar]
  57. Luo, X.-L.; Xu, J.-J.; Zhao, W.; Chen, H.-Y. Glucose Biosensor Based on ENFET Doped with SiO2 Nanoparticles. Sens. Actuator B-Chem 2004, 97, 249–255. [Google Scholar]
  58. Shoji, E.; Freund, M.S. Potentiometric Saccharide Detection Based on the pKa Changes of Poly(aniline boronic acid). J. Am. Chem. Soc 2002, 124, 12486–12493. [Google Scholar]
  59. Shoji, E.; Freund, M.S. Potentiometric Sensors Based on the Inductive Effect on the pKa of Poly(aniline): A Nonenzymatic Glucose Sensor. J. Am. Chem. Soc 2001, 123, 3383–3384. [Google Scholar]
  60. Wang, J. Amperometric Biosensors for Clinical and Therapeutic Drug Monitoring: A Review. J. Pharm. Biomed. Anal 1999, 19, 47–53. [Google Scholar]
  61. Park, S.; Boo, H.; Chung, T.D. Electrochemical Non-Enzymatic Glucose Sensors. Anal. Chim. Acta 2006, 556, 46–57. [Google Scholar]
  62. Immobilized Enzyme in Analytical Chemistry. In Advances In Biochemical Engineering/Biotechnology; Carr, P.W.; Browers, L.D. (Eds.) Springer Berlin: Heidelberg, Germany, 1980; pp. 89–129.
  63. Cass, A.E.G.; Davis, G.; Francis, G.D.; Hill, H.A.O.; Aston, W.J.; Higgins, I.J.; Plotkin, E.V.; Scott, L.D.L.; Turner, A.P.F. Ferrocene-Mediated Enzyme Electrode for Amperometric Determination of Glucose. Anal. Chem 1984, 56, 667–671. [Google Scholar]
  64. Liu, S.; Ju, H. Reagentless Glucose Biosensor Based On Direct Electron Transfer of Glucose Oxidase Immobilized on Colloidal Gold Modified Carbon Paste Electrode. Biosens. Bioelectron 2003, 19, 177–183. [Google Scholar]
  65. Yi, X.; Patolsky, F.; Katz, E.; Hainfeld, J.F.; Willner, I. Plugging into Enzymes: Nanowiring of Redox Enzymes by a Gold Nanoparticle. Science 2003, 299, 1877–1881. [Google Scholar]
  66. Basu, S.; Kang, W.P.; Davidson, J.L.; Choi, B.K.; Bonds, A.B.; Cliffel, D.E. Electrochemical Sensing Using Nanodiamond Microprobe. Diam. Relat. Mat 2006, 15, 269–274. [Google Scholar]
  67. Yang, H.; Zhu, Y. Size Dependence of SiO2 Particles Enhanced Glucose Biosensor. Talanta 2006, 68, 569–574. [Google Scholar]
  68. Zang, J.; Li, C.M.; Cui, X.; Wang, J.; Sun, X.; Chang, H.D.; Sun, Q. Tailoring Zinc Oxide Nanowires for High Performance Amperometric Glucose Sensor. Electroanalysis 2007, 19, 1008–1014. [Google Scholar]
  69. Liu, X.W.; Hu, Q.; Wu, Q.; Zhang, W.; Fang, Z.; Xie, Q. Aligned ZnO Nanorods: A Useful Film to Fabricate Amperometric Glucose Biosensor. Colloid Surf. B-Biointerfaces 2009, 74, 154–158. [Google Scholar]
  70. Bai, Y.; Sun, Y.; Sun, C. Pt–Pb Nanowire Array Electrode for Enzyme-Free Glucose Detection. Biosens. Bioelectron 2008, 24, 579–585. [Google Scholar]
  71. Salimi, A.; Roushani, M. Non-enzymatic Glucose Detection Free of Ascorbic Acid Interference Using Nickel Powder and Nafion Sol-Gel Dispersed Renewable Carbon Ceramic Electrode. Electrochem. Commun 2005, 7, 879–887. [Google Scholar]
  72. Wang, J.; Thomas, D.F.; Chen, A. Nonenzymatic Electrochemical Glucose Sensor Based on Nanoporous PtPb Networks. Anal. Chem 2008, 80, 997–1004. [Google Scholar]
  73. Li, Y.; Song, Y.-Y.; Yang, C.; Xia, X.-H. Hydrogen bubble Dynamic Template Synthesis of Porous Gold for Nonenzymatic Electrochemical Detection of Glucose. Electrochem. Commun 2007, 9, 981–988. [Google Scholar]
  74. Safavi, A.; Maleki, N.; Farjami, E. Fabrication of a Glucose Sensor Based On a Novel Nanocomposite Electrode. Biosens. Bioelectron 2009, 24, 1655–1660. [Google Scholar]
  75. You, T.; Niwa, O.; Tomita, M.; Ando, H.; Suzuki, M.; Hirono, S. Characterization and Electrochemical Properties of Highly Dispersed Copper Oxide/Hydroxide Nanoparticles in Graphite-like Carbon Films Prepared by RF Sputtering Method. Electrochem. Commun 2002, 4, 468–471. [Google Scholar]
  76. Guan, J.G.; Miao, Y.Q.; Zhang, Q.J. Impedemetric Biosensor. J. Biosci. Bioeng 2004, 97, 219–226. [Google Scholar]
  77. Fuchs, K.; Kaatze, U. Molecular Dynamics Of Carbohydrate Aqueous Solutions. Dielectric Relaxation as a Function of Glucose and Fructose Concentration. J. Phys. Chem., Sect. B 2001, 105, 2036–2042. [Google Scholar]
  78. Caduff, A.; Hirt, E.; Feldman, Y.; Ali, Z.; Heinemann, L. First Human Experiments with a Novel Non-Invasive, Non-Optical Continuous Glucose Monitoring System. Biosens. Bioelectron 2003, 19, 209–217. [Google Scholar]
  79. Shervedani, R.K.; Mehrjardi, A.H.; Zamiri, N. A Novel Method for Glucose Determination Based On Electrochemical Impedance Spectroscopy Using Glucose Oxidase Self-Assembled Biosensor. Bioelectrochemistry 2006, 69, 201–208. [Google Scholar]
  80. Forzani, E.S.; Zhang, H.; Nagahara, L.A.; Amlani, I.; Tsui, R.; Tao, N. A Conducting Polymer Nanojunction Sensor for Glucose Detection. Nano Lett 2004, 9, 1785–1788. [Google Scholar]
  81. Besteman, K.; Lee, J.-O.; Wiertz, F.G.M.; Heering, H.A.; Dekker, C. Enzyme-Coated Carbon Nanotubes as Single-Molecule Biosensors. Nano Lett 2003, 3, 727–730. [Google Scholar]
  82. Ansari, S.G.; Ansari, Z.A.; Wahab, R.; Kim, Y.-S.; Khang, G.; Shin, H.-S. Glucose Sensor Based On Nano-Baskets of Tin Oxide Templated in Porous Alumina By Plasma Enhanced CVD. Biosens. Bioelectron 2008, 23, 1838–1842. [Google Scholar]
  83. Yang, K.; She, G.-W.; Wang, H.; Ou, X.-M.; Zhang, X.-H.; Lee, C.-S.; Lee, S.-T. ZnO Nanotube Arrays as Biosensors for Glucose. J. Phys. Chem. C 2009, 113, 20169–20172. [Google Scholar]
  84. Zhang, F.F; Wang, X.; Ai, S.; Sun, Z.; Wan, Q.; Zhu, Z.; Xian, Y.; Jin, L.; Yamamoto, K. Immobilization of Uricase on ZnO Nanorods for a Reagentless Uric Acid Biosensor. Anal. Chimi. Acta 2004, 519, 155–160. [Google Scholar]
  85. Zhao, J.; Wu, D.; Zhi, J. A Novel Tyrosinase Biosensor Based On Biofunctional ZnO Nanorod Microarrays on the Nanocrystalline Diamond Electrode for Detection of Phenolic Compounds. Bioelectrochemistry 2009, 75, 44–49. [Google Scholar]
  86. Rodriguez, J.A.; Jirsak, T.; Dvorak, J.; Sambasivan, S.; Fischer, D. Reaction of NO2 with Zn and ZnO: Photoemission, XANES, and Density Functional Studies on the Formation of NO3. J. Phys. Chem. B 2000, 104, 319–328. [Google Scholar]
  87. Tian, Z.R.; Voigt, J.A.; Liu, J.; Mckenzie, B.; Mcdermott, M. J. Biomimetic Arrays of Oriented Helical ZnO Nanorods and Columns. J. Am. Chem. Soc 2002, 124, 12954–12955. [Google Scholar]
  88. Wei, A.; Suna, X.W.; Wang, J.X.; Lei, Y.; Cai, X.P.; Li, C.M.; Dong, Z.L.; Huang, W. Enzymatic Glucose Biosensor Based On ZnO Nanorod Array Grown by Hydrothermal Decomposition. Appl. Phys. Lett 2006, 89. [Google Scholar]
  89. Kang, B.S.; Wang, H.T.; Ren, F.; Pearton, S.J.; Morey, T.E.; Dennis, D.M.; Johnson, J.W.; Rajagopal, P.; Roberts, J.C.; Piner, E.L.; Linthicum, K.J. Enzymatic Glucose Detection Using ZnO Nanorods on the Gate Region of AlGaN/GaN High Electron Mobility Transistors. Appl. Phys. Lett 2007, 91. [Google Scholar]
  90. Kim, J.S.; Park, W.; Lee, C.-H.; Yi, G-C. ZnO Nanorod Biosensor for Highly Sensitive Detection of Specific Protein Binding. J. Korean Phys. Soc 2006, 49, 1–5. [Google Scholar]
  91. Zhao, Z.W.; Chen, X.J.; Tay, B.K.; Chen, J.S.; Han, Z.J.; Khor, K.A. A Novel Amperometric Biosensor Based On ZnO: Co Nanoclusters For Biosensing Glucose. Biosens. Bioelectron 2007, 23, 135–139. [Google Scholar]
  92. Dai, Z.; Shao, G.; Hong, J.; Bao, J.; Shen, J. Immobilization and Direct Electrochemistry of Glucose Oxidase on a Tetragonal Pyramid-Shaped Porous ZnO Nanostructure for a Glucose Biosensor. Biosens. Bioelectron 2009, 24, 1286–1291. [Google Scholar]
  93. Kong, T.; Chen, Y.; Ye, Y.; Zhang, K.; Wang, Z.; Wang, X. An Amperometric Glucose Biosensor Based On the Immobilization of Glucose Oxidase on the ZnO Nanotubes. Sens. Actuator B-Chem 2009, 138, 344–350. [Google Scholar]
  94. Wang, J.X.; Sun, X.W.; Wei, A.; Lei, Y.; Cai, X.P.; Li, C.M.; Dong, Z.L. Zinc Oxide Nanocomb Biosensor for Glucose Detection. Appl. Phys. Lett 2006, 88. [Google Scholar]
  95. Liu, J.; Guo, C.; Li, C.M.; Li, Y.; Chi, Q.; Huang, X.; Liao, L.; Yu, T. Carbon-Decorated ZnO Nanowire Array: A Novel Platform for Direct Electrochemistry of Enzymes and Biosensing Applications. Electrochem. Commun 2009, 11, 202–205. [Google Scholar]
  96. Lin, Y.; Lu, F.; Tu, Y.; Ren, Z. Glucose biosensors Based on Carbon Nanotube Nanoelectrode Ensembles. Nano Lett 2004, 4, 191–195. [Google Scholar]
  97. Sun, W.; Gao, R.; Jiao, K. Electrochemistry and Electrocatalysis of Hemoglobin in Nafion/nano-CaCO3 Film on a New Ionic Liquid BPPF6 Modified Carbon Paste Electrode. J. Phys. Chem. B 2007, 111, 4560–4567. [Google Scholar]
  98. Sheng, Q.; Luo, K.; Li, L.; Zheng, J. Direct Electrochemistry of Glucose Oxidase Immobilized on NdPO4 Nanoparticles/Chitosan Composite Film on Glassy Carbon Electrodes and Its Biosensing Application. Bioelectrochemistry 2009, 74, 246–253. [Google Scholar]
  99. Bordonaba, V.L.; Terry, V. Development of a Glucose Biosensor for Rapid Assessment of Strawberry Quality: Relationship between Biosensor Response and Fruit Composition. J. Agric. Food Chem 2009, 57, 8220–8226. [Google Scholar]
  100. Wang, Y.-T.; Yu, L.; Zhu, Z.-Q.; Zhang, J.; Zhu, J.-Z.; Fan, C.-H. Improved Enzyme Immobilization for Enhanced Bioelectrocatalytic Activity of Glucose Sensor. Sens. Actuator B-Chem 2009, 136, 332–337. [Google Scholar]
  101. Koschinsky, T.; Heinemann, L. Sensors for Glucose Monitoring: Technical and Clinical Aspects. Diabetes Metab Res Rev 2001, 17, 113–123. [Google Scholar]
  102. Bantle, J.P.; Thomas, W. Glucose Measurement in Patients with Diabetes Mellitus with Dermal Interstitial Fluid. J. Lab. Clin. Med 1997, 130, 436–441. [Google Scholar]
  103. Bolinder, J.; Hagstrom, E.; Ungerstedt, U.; Arner, P. Microdialysis of Subcutaneous Adipose Tissue in Vivo for Continuous Glucose Monitoring in Man. Scand J. Clin. Lab. Invest 1989, 49, 465–474. [Google Scholar]
  104. Asif, M.H.; Ali, S.M.U.; Nur, O.; Willander, M.; Brannmark, C.; Stralfors, P.; Englund, U.H.; Elinder, F.; Danielsson, B. Functionalised ZnO-nanorod-based Selective Electrochemical Sensor for Intracellular Glucose. Biosens. Bioelectron 2010, in press. [Google Scholar] [CrossRef]
  105. Mho, S.I.; Johnson, D.C. Electrocatalytic Response of Carbohydrates at Copper-Alloy Electrodes. J. Electroanal. Chem 2001, 500, 524–532. [Google Scholar]
  106. Salimi, A.; Roushani, M. Non-enzymatic Glucose Detection Free of Ascorbic Acid Interference Using Nickel Powder and Nafion Sol–Gel Dispersed Renewable Carbon Ceramic Electrode. Electrochem. Commun 2005, 7, 879–887. [Google Scholar]
  107. Jiang, X.; Herricks, T.; Xia, Y. CuO Nanowires Can Be Synthesized by Heating Copper Substrates in Air. Nano Lett 2002, 2, 1333–1338. [Google Scholar]
  108. Wang, D.; Song, C.; Hu, Z.; Fu, X. Fabrication of Hollow Spheres and Thin Films of Nickel Hydroxide and Nickel Oxide with Hierarchical Structures. J. Phys. Chem. B 2005, 109, 1125–1129. [Google Scholar]
  109. Gao, X.P.; Bao, J.L.; Pan, G.L.; Zhu, H.Y.; Huang, P.X.; Wu, F.; Song, D.Y. Preparation and Electrochemical Performance of Polycrystalline and Single Crystalline CuO Nanorods as Anode Materials for Li Ion Battery. J. Phys. Chem. B 2004, 108, 5547–5551. [Google Scholar]
  110. Zhang, J.; Liu, J.; Peng, Q.; Wang, X.; Li, Y. Nearly Monodisperse Cu2O and CuO Nanospheres: Preparation and Applications for Sensitive Gas Sensors. Chem. Mater 2006, 18, 867–871. [Google Scholar]
  111. Rakhshani, A.E.; Makdisi, Y.; Mathew, X. Deep Energy Levels and Photoelectrical Properties of Thin Cuprous Oxide Films. Thin Solid Films 1996, 288, 69–75. [Google Scholar]
  112. McAuley, C.B; Du, Y.; Wildgoose, G.G.; Compton, R.G. The use of Copper(II) Oxide Nanorod Bundles for the Non-Enzymatic Voltammetric Sensing of Carbohydrates and Hydrogen Peroxide. Sens. Actuat. B-Chem 2008, 135, 230–235. [Google Scholar]
  113. Wang, W.; Li, Z.; Zheng, W.; Yang, J.; Zhang, H.; Wang, C. Electrospun Palladium (IV)-doped Copper Oxide Composite Nanofibers for Non-Enzymatic Glucose Sensors. Electrochem. Commun 2009, 11, 1811–1814. [Google Scholar]
  114. Yeo, I.H.; Johnson, D.C. Anodic Response of Glucose at Copper-Based Alloy Electrodes. J. Electroanal. Chem 2000, 484, 157–163. [Google Scholar]
  115. Wang, W.; Zhang, L.; Tong, S.; Li, X.; Song, W. Three-Dimensional Network Films of Electrospun Copper Oxide Nanofibers for Glucose Determination. Biosens. Bioelectron 2009, 25, 708–714. [Google Scholar]
  116. Zhuang, Z.; Su, X.; Yuan, H.; Sun, Q.; Xiao, D.; Choi, M.M.F. An improved Sensitivity Non-Enzymatic Glucose Sensor Based on a CuO Nanowire Modified Cu Electrode. Analyst 2008, 133, 126–132. [Google Scholar]
  117. Auley, C.B.M.; Wildgoose, G.G.; Compton, R.G.; Shao, L.D.; Green, M.L.H. Copper Oxide Nanoparticle Impurities Are Responsible for the Electroanalytical Detection of Glucose Seen Using Multiwalled Carbon Nanotubes. Sens. Actuat. B-Chem 2008, 132, 356–360. [Google Scholar]
  118. Zhang, X.; Wang, G.; Zhang, W.; Wei, Y.; Fang, B. Fixure-reduce Method for the Synthesis of Cu2O/MWCNTs Nanocomposites and Its Application as Enzyme-Free Glucose Sensor. Biosens. Bioelectron 2009, 24, 3395–3398. [Google Scholar]
  119. Jiang, L.-C.; Zhang, W.-D. A Highly Sensitive Nonenzymatic Glucose Sensor Based on CuO Nanoparticles-Modified Carbon Nanotube Electrode. Biosens. Bioelectron 2010, 25, 1402–1407. [Google Scholar]
  120. Panzner, G.; Egert, B.; Schmidt, H.P. The Stability of CuO and Cu2O Surfaces During Argon Sputtering Studied by XPS and AES. Surf. Sci 1984, 151, 400–408. [Google Scholar]
  121. Luque, G.L.; Rodriguez, M.C.; Rivas, G.A. Glucose Biosensors Based on the Immobilization of Copper Oxide and Glucose Oxidase within a Carbon Paste Matrix. Talanta 2005, 66, 467–471. [Google Scholar]
  122. Umar, A.; Rahman, M.M.; Al-Hajry, A.; Hahn, Y.-B. Enzymatic Glucose Biosensor Based on Flower-Shaped Copper Oxide Nanostructures Composed of Thin Nanosheets. Electrochem. Commun 2009, 11, 278–281. [Google Scholar]
  123. Karyakin, A.A.; Karyakina, E.E.; Gorton, L. Amperometric Biosensor for Glutamate Using Prussian Blue-Based “Artificial Peroxidase” as a Transducer for Hydrogen Peroxide. Anal. Chem 2000, 72, 1720–1723. [Google Scholar]
  124. Hoshi, T.; Saiki, H.; Kuwazawa, S.; Tsuchiya, C.; Chen, Q.; Anzai, J.-I. Selective Permeation of Hydrogen Peroxide through Polyelectrolyte Multilayer Films and Its Use for Amperometric Biosensors. Anal. Chem 2001, 73, 5310–5315. [Google Scholar]
  125. Muguruma, H.; Hiratsuka, A.; Karube, I. Thin-Film Glucose Biosensor Based on Plasma-Polymerized Film: Simple Design for Mass Production. Anal. Chem 2000, 72, 2671–2675. [Google Scholar]
  126. Xu, J.-J.; Yu, Z.-H.; Chen, H.-Y. Glucose Biosensors Prepared by Electropolymerization of p-Chlorophenylamine with and without Nafion. Anal. Chim. Acta 2002, 463, 239–247. [Google Scholar]
  127. Pandey, P.C.; Upadhyay, S.; Shukla, N.K.; Sharma, S. Studies on the Electrochemical Performance of Glucose Biosensor Based on Ferrocene Encapsulated ORMOSIL and Glucose Oxidase Modified Graphite Paste Electrode. Biosens. Bioelectron 2003, 18, 1257–1268. [Google Scholar]
  128. Krikstopaitis, K.; Kulys, J.; Tetianec, L. Bioelectrocatalytical Glucose Oxidation with Phenoxazine Modified Glucose Oxidase. Electrochem.Commun 2004, 6, 331–336. [Google Scholar]
  129. Elizabeth, A.H.H.; Gooding, J.J.; Hall, C.E. Redox Enzyme Linked Electrochemical Sensors: Theory Meets Practice. Mikrochim. Acta 1995, 121, 119–145. [Google Scholar]
  130. Luo, X.-L.; Xu, J.-J.; Zhao, W.; Chen, H.-Y. Ascorbic Acid Sensor Based on Ion-Sensitive Field-Effect Transistor Modified with MnO2 Nanoparticles. Electrochem. Commun 2004, 6, 1169–1173. [Google Scholar]
  131. Kim, D.W.; Hong, Y.K.; Lee, N-S.; Kim, C.S.; Jeon, B.K.; Kang, B.M. Seperation of Magnesium Isotopes by Chemical Exchange with Manganese(IV) Oxide. J. Nucl. Sci. Technol 2001, 38, 780–784. [Google Scholar]
  132. Russo, F.; Johnson, C.J.; Johnson, C.J.; McKenzie, D.; Aiken, J.M.; Pedersen, J.A. Pathogenic Prion Protein Is Degraded by a Manganese Oxide Mineral Found in Soils. J. Gen. Virol 2009, 90, 275–280. [Google Scholar]
  133. Turkusic, E.; Kalcher, K.; Schachl, K.; Komersova, A.; Bartos, M.; Moderegger, H.; Svancara, I.; Vytras, K. Amperometric Determination of Glucose with an MnO2 and Glucose Oxidase Bulk-Modified Screen-Printed Carbon Ink Biosensor. Anal.Lett. 2001, 34, 2633–2647. [Google Scholar]
  134. Xu, J.-J.; Feng, J.-J.; Zhong, X.; Chen, H.-Y. Low-Potential Detection of Glucose with a Biosensor Based on the Immobilization of Glucose Oxidase on Polymer/Manganese Oxide Layered Nanocomposite. Electroanalysis 2008, 20, 507–512. [Google Scholar]
  135. Xu, J.-J.; Luo, X.-L.; Du, Y.; Chen, H.-Y. Application of MnO2 Nanoparticles as an Eliminator of Ascorbate Interference to Amperometric Glucose Biosensors. Electrochem. Commun 2004, 6, 1169–1173. [Google Scholar]
  136. Chen, J.; Zhang, W.-D.; Ye, J.-S. Nonenzymatic Electrochemical Glucose Sensor Based on MnO2/MWNTs Nanocomposites. Electrochem. Commun 2008, 10, 1268–1271. [Google Scholar]
  137. Mathur, S.; Erdemc, A.; Cavelius, C.; Barth, S.; Altmayer, J. Amplified Electrochemical DNA-Sensing of Nanostructured Metal Oxide Filmsdeposited on Disposable Graphite Electrodes Functionalized by Chemical Vapor Deposition. Sens. Actuat. B-Chem 2009, 136, 432–437. [Google Scholar]
  138. Durrant, J.R. Protein Adsorption on Nanocrystalline TiO2 Film: An Immobilization Strategy for Bioanalytical Devices. Anal. Chem 1998, 70, 5111–5113. [Google Scholar]
  139. Seo, D-W.; Sarker, S.; Deb Nath, N.C.; Choi, S-W.; Ahammad, A.J.S.; Lee, J.-J.; Kim, W.-G. Synthesis of a Novel Imidazolium –Based Electrolytes and Application for Dye-Sensitized Solar Cell. Electrochim. Acta 2010, 55, 1483–1488. [Google Scholar]
  140. Tian, M.; Wu, G.; Adams, B.; Wen, J.; Chen, A. Kinetics of Photoelectrocatalytic Degradation of Nitrophenols on Nanostructured TiO2 Electrodes. J. Phys. Chem. C 2008, 112, 825–831. [Google Scholar]
  141. Lucarelli, L.; Nadtochenko, V.; Kiwi, J. Environmental Photochemistry: Quantitative Adsorption and FTIR Studies during the TiO2-Photocatalyzed Degradation of Orange II. Langmuir 2000, 16, 1102–1108. [Google Scholar]
  142. Kavan, L.; Rathousky, J.; Gra1tzel, M.; Shklover, V.; Zukal, A. Surfactant-Templated TiO2 (Anatase): Characteristic Features of Lithium Insertion Electrochemistry in Organized Nanostructures. J. Phys. Chem. B 2000, 104, 12012–12020. [Google Scholar]
  143. Shen, Q.; You, S.-K.; Park, S.-G.; Jiang, H.; Guo, D.; Chen, B.; Wang, X. Electrochemical Biosensing for Cancer Cells Based on TiO2/CNT Nanocomposites Modified Electrodes. Electroanalysis 2008, 20, 2526–2530. [Google Scholar]
  144. Kurokawa, Y.; Sano, T.; Ohta, H.; Nakagawa, Y. Immobilization of Enzyme onto Cellulose-Titanium Oxide Composite Fiber. Biotechnol. Bioeneng 1993, 42, 394–397. [Google Scholar]
  145. Kennedy, J.F.; Kay, I.M. Hydrous Titanium Oxides—/New Supports for the Simple Immobilization of Enzymes. J. Chem. Soc. Perkin Trans 1976, 1, 329–335. [Google Scholar]
  146. Lev, O.; Tsionsky, M.; Rabinovich, L.; Glezer, V.; Sampath, S.; Pankratov, I.; Gun, J. Organically Modified Sol-Gel Sensor. Anal. Chem 1995, 67, 22A–30A. [Google Scholar]
  147. Gill, I. Bio-doped Nanocomposite Polymers: Sol-Gel Bioencapsulates. Chem. Mater 2001, 13, 3404–3421. [Google Scholar]
  148. Walcarius, A. Electrochemical Applications of Silica-Based Organic-Inorganic Hybrid Materials. Chem. Mater 2001, 13, 3351–3372. [Google Scholar]
  149. Choi, H.N.; Kim, M.A.; Lee, W.-Y. Amperometric Glucose Biosensor Based on Sol–Gel-Derived Metal Oxide/Nafion Composite Films. Anal.Chim. Acta 2005, 537, 179–187. [Google Scholar]
  150. Guo, B.; Liu, Z.; Hong, L.; Jiang, H. Sol-gel Derived Photocatalytic Porous TiO2 Thin Films. Surf. Coat. Technol 2005, 198, 24–29. [Google Scholar]
  151. Shu, X.; Chen, Y.; Yuan, H.; Gao, S.; Xiao, D. H2O2 Sensor Based on the Room-Temperature Phosphorescence of Nano TiO2/SiO2 Composite. Anal. Chem 2007, 79, 3695–3702. [Google Scholar]
  152. Xu, X.; Zhao, J.; Jiang, D.; Kong, J.; Liu, B.; Deng, J. TiO2 Sol-Gel Derived Amperometric Biosensor for H2O2 on the Electropolymerized Phenazine Methosulfate Modified Electrode. Anal. Bioanal. Chem 2002, 374, 1261–1266. [Google Scholar]
  153. Wang, R.; Ruan, C.; Kanayeva, D.; Lassiter, K.; Li, Y. TiO2 Nanowire Bundle Microelectrode Based Impedance Immunosensor for Rapid and Sensitive Detection of Listeria monocytogenes. Nano Lett 2008, 8, 2625–2631. [Google Scholar]
  154. Yuan, S.; Hu, S. Characterization and Electrochemical Studies of Nafion/nano-TiO2 Film Modified Electrodes. Electrochim. Acta 2004, 49, 4287–4293. [Google Scholar]
  155. Yang, D.-H.; Takahara, N.; Lee, S.-W.; Kunitake, T. Fabrication of Glucose-Sensitive TiO2 Ultrathin Films by Molecular Imprinting and Selective Detection of Monosaccharides. Sens. Actuat. B-Chem 2008, 130, 379–385. [Google Scholar]
  156. Viticoli, M.; Curulli, A.; Cusma, A.; Kaciulis, S.; Nunziante, S.; Pandolfi, L.; Valentini, F.; Padeletti, G. Third-Generation Biosensors Based on TiO2 Nanostructured Films. Mater. Sci. Eng. C 2006, 26, 947–951. [Google Scholar]
  157. Bao, S.-J.; Li, C.M.; Zang, J.-F.; Cui, X.-Q.; Qiao, Y.; Guo, J. New Nanostructured TiO2 for Direct Electrochemistry and Glucose Sensor Applications. Adv. Funct. Mater 2008, 18, 591–599. [Google Scholar]
  158. Russell, R.J.; Pishko, M.V.; Gefrides, C.C.; McShane, M.J.; Cote, G.L. A Fluorescence-Based Glucose Biosensor Using Concanavalin A and Dextran Encapsulated in a Poly(ethylene glycol) Hydrogel. Anal. Chem 1999, 71, 3126–3132. [Google Scholar]
  159. Grant, S.A.; Glass, R.S. A Sol–Gel Based Fiber Optic Sensor for Local Blood pH Measurement. Sens. Actuat.-B- Chem 1997, 45, 35–42. [Google Scholar]
  160. Gulcev, M.D.; Goring, G.L.G.; Rakic, M.; Brennan, J.D. Reagentless pH Based Biosensing Using a Fluorescently-Labeled Dextran Co-Entrapped with a Hydrolytic Enzyme in Sol–Gel Derived Nanocomposite Films. Anal. Chim. Acta 2002, 457, 47–59. [Google Scholar]
  161. Doong, R.; Shih, H.-M. Glutamate Optical Biosensor Based on the Immobilization of Glutamate Dehydrogenase in Titanium Dioxide Sol–Gel Matrix. Biosens. Bioelectron 2006, 22, 185–191. [Google Scholar]
  162. Yang, X.; Zhoua, Z.; Xiao, D.; Choi, M.M.F. A Fluorescent Glucose Biosensor Based on Immobilized Glucose Oxidase on Bamboo Inner Shell Membrane. Biosens. Bioelectron 2006, 21, 1613–1620. [Google Scholar]
  163. Yonzon, C.R.; Haynes, C.L.; Zhang, X.; Walsh, J.T.; Duyne, R.P.V. A Glucose Biosensor Based on Surface-Enhanced Raman Scattering: Improved Partition Layer, Temporal Stability, Reversibility, and Resistance to Serum Protein Interference. Anal. Chem 2004, 76, 78–85. [Google Scholar]
  164. Doong, R.; Shih, H.-M. Array-Based Titanium Dioxide Biosensors for Ratiometric Determination of Glucose, Glutamate and Urea. Biosens. Bioelectron 2010, 25, 1439–1446. [Google Scholar]
  165. Feng, K.-J.; Yang, Y.-H.; Wang, Z.-J.; Jiang, J.-H.; Shen, G.-L.; Yu, R.-Q. A Nano-Porous CeO2/Chitosan Composite Film as the Immobilization Matrix for Colorectal Cancer DNA Sequence-Selective Electrochemical Biosensor. Talanta 2006, 70, 561–565. [Google Scholar]
  166. Tarnuzzer, R.W.; Colon, J.; Patil, S.; Seal, S. Vacancy Engineered Ceria Nanostructures for Protection from Radiation-Induced Cellular Damage. Nano Lett 2005, 5, 2573–2577. [Google Scholar]
  167. Zhang, W.; Yang, T.; Zhuang, X.; Guo, Z.; Jiao, K. An Ionic Liquid Supported CeO2 Nanoshuttles–Carbon Nanotubes Composite as a Platform for Impedance DNA Hybridization Sensing. Biosens. Bioelectron 2009, 24, 2417–2422. [Google Scholar]
  168. Gojova, A.; Lee, J.-T.; Jung, H.S.; Guo, B.; Barakat, A.I.; Kennedy, I.M. Effect of Cerium Oxide Nanoparticles on Inflammation in Vascular Endothelial cells. Inhal. Toxicol 2009, 21, 123–130. [Google Scholar]
  169. Njagi, J.; Ispas, C.; Andreescu, S. Mixed Ceria-Based Metal Oxides Biosensor for Operation in Oxygen Restrictive Environments. Anal. Chem 2008, 80, 7266–7274. [Google Scholar]
  170. Ansari, A.A.; Solanki, P.R.; Malhotra, B.D. Hydrogen Peroxide Sensor Based on Horseradish Peroxidase Immobilized Nanostructured Cerium Oxide Film. J. Biotechnol 2009, 142, 179–184. [Google Scholar]
  171. Ansari, A.A.; Kaushik, A.; Solanki, P.R.; Malhotra, B.D. Sol–gel Derived Nanoporous Cerium Oxide Film for Application to Cholesterol Biosensor. Electrochem. Commun 2008, 10, 1246–1249. [Google Scholar]
  172. Solanki, P.R.; Dhand, C.; Kaushik, A.; Ansari, A.A.; Sood, K.N.; Malhotra, B.D. Nanostructured Cerium Oxide Film for Triglyceride Sensor. Sens. Actuat. B-Chem 2009, 141, 551–556. [Google Scholar]
  173. Malhotra, B.D.; Kaushik, A. Metal Oxide–Chitosan Based Nanocomposite for Cholesterol Biosensor. Thin Solid Films 2009, 518, 614–620. [Google Scholar]
  174. Ispas, C.; Njagi, J.; Cates, M.; Andreescu, S. Electrochemical Studies of Ceria as Electrode Material for Sensing and Biosensing Applications. J. Electrochem. Soc 2008, 155, F169–F176. [Google Scholar]
  175. Rodriguez, J.A.; Liu, S.M.P.; Hrbek, J.; Evans, J.; Pérez, M. Activity of CeOx and TiOx Nanoparticles Grown on Au(111) in the Water-Gas Shift Reaction. Science 2007, 318, 1757–1759. [Google Scholar]
  176. Saha, S.; Arya, S.K.; Singh, S.P.; Sreenivas, K.; Malhotra, B.D.; Gupta, V. Nanoporous Cerium Oxide Thin Film for Glucose Biosensor. Biosens. Bioelectron 2009, 24, 2040–2045. [Google Scholar]
  177. Chettibi, S.; Wojcieszak, R.; Boudjennad, E.H.; Belloni, J.; Bettahar, M.M.; Keghouche, N. Ni–Ce Intermetallic Phases in CeO2-supported Nickel Catalysts Synthesized by G-Radiolysis. Catalysis Today 2006, 113, 157–165. [Google Scholar]
  178. Sigler, P.; Masters, B.J. The Hydrogen Peroxide-induced Ce*(III)-Ce(IV) Exchange System. J. Am. Chem. Soc 1957, 79, 6353–6357. [Google Scholar]
  179. Ansari, A.A.; Solanki, P.R.; Malhotra, B.D. Sol-gel Derived Nanostructured Cerium Oxide Film for Glucose Sensor. Appl. Phys. Lett 2008, 92. [Google Scholar]
  180. Wu, Q.; Zhang, F.; Xiao, P.; Tao, H.; Wang, X.; Hu, Z. Great Influence of Anions for Controllable Synthesis of CeO2 Nanostructures: From Nanorods to Nanocubes. J. Phys. Chem. C 2008, 112, 17076–17080. [Google Scholar]
  181. Zhou, H.-P.; Zhang, Y.-W.; Mai, H.-X.; Sun, X.; Liu, Q.; Song, W.-G.; Yan, C.-H. Spontaneous Organization of Uniform CeO2 Nanoflowers by 3D Oriented Attachment in Hot Surfactant Solutions Monitored with an In Situ Electrical Conductance Technique. Chem. Eur. J 2008, 14, 3380–3390. [Google Scholar]
  182. Manesh, K.M; Kim, J,H.; Santhosh, P.; Gopalan, A.I.; Lee, K.P.; Kang, H.D. Fabrication of a Gold Nanoparticles Decorated Carbon Nanotubes Based Novel Modified Electrode for the Electrochemical Detection of Glucose. J. Nanosci. Nanotechnol 2007, 7, 3365–3372. [Google Scholar]
  183. Ragupathy, D.; Gopalan, A.I.; Lee, K.P. Synergistic Contributions of Multiwall Carbon Nanotubes and Gold Nanoparticles in a Chitosan–Ionic Liquid Matrix towards Improved Performance for a Glucose Sensor. Electrochem Commun 2009, 11, 397–401. [Google Scholar]
  184. Gopalan, A.I.; Lee., K.P.; Manesh, K.M.; Santhosh, P.; Kim, J.H.; Kang, J.S. Electrochemical Determination of Dopamine and Ascorbic Acid at a Novel Gold Nanoparticles Distributed Poly(4-aminothiophenol) Modified Electrode. Talanta 2007, 71, 1774–1781. [Google Scholar]
  185. Kang, X.; Wang, J.; Tang, Z.; Wu, H.; Lin, Y. Direct Electrochemistry and Electrocatalysis of Horseradish Peroxidase Immobilized in Hybrid Organic–Inorganic Film of Chitosan/Sol–Gel/Carbon Nanotubes. Talanta 2009, 78, 120–125. [Google Scholar]
  186. Wu, S.; Ju, H.; Liu, Y. Conductive Mesocellular Silica–Carbon Nanocomposite Foams for Immobilization, Direct Electrochemistry, and Biosensing of Proteins. Adv. Funct. Mater 2007, 17, 585–592. [Google Scholar]
  187. Yang, H.; Zhu, Y. Glucose biosensor Based on nano-SiO2 and “unprotected” Pt nanoclusters. Biosens. Bioelectron 2007, 22, 2989–2993. [Google Scholar]
  188. Li, Y.; Liu, X.; Yuan, H.; Xiao, D. Glucose Biosensor Based on the Room-Temperature Phosphorescence of TiO2/SiO2 Nanocomposite. Biosens. Bioelectron 2009, 24, 3706–3710. [Google Scholar]
  189. Liang, R.P.; Jiang, J.L.; Qiu, J.D. Preparation of GOD/sol–gel Silica Film on Prussian Blue Modified Electrode for Glucose Biosensor Application. Electroanalysis 2008, 20, 2642–2648. [Google Scholar]
  190. Zou, Y.; Xiang, C.; Suna, L.-X.; Xu, F. Glucose Biosensor Based on Electrodeposition of Platinum Nanoparticles onto Carbon Nanotubes and Immobilizing Enzyme with Chitosan-SiO2 Sol–Gel. Biosens. Bioelectron 2008, 23, 1010–1016. [Google Scholar]
  191. Patel, A.C.; Li, S.; Yuan, J.-M.; Wei, Y. In Situ Encapsulation of Horseradish Peroxidase in Electrospun Porous Silica Fibers for Potential Biosensor Applications. Nano Lett 2006, 6, 1042–1046. [Google Scholar]
  192. Gopalan, A.I.; Lee, K.P.; Ragupathy, D.; Lee, S.H.; Lee, J.W. An Electrochemical Glucose Biosensor Exploiting a Polyaniline Grafted Multiwalled Carbon Nanotube/Perfluorosulfonate Ionomer–Silica Nanocomposites. Biomaterials 2009, 30, 5999–6005. [Google Scholar]
  193. Qiua, B.; Lina, Z.; Wanga, J.; Chena, Z.; Chena, J.; Chen, G. An Electrochemiluminescent Biosensor for Glucose Based on the Electrochemiluminescence of Luminol on the Nafion/Glucoseoxidase/Poly(nickel(II)tetrasulfo phthalocyanine)/multi-walled Carbon Nanotubes Modified Electrode. Talanta 2009, 78, 76–80. [Google Scholar]
  194. Jia, J.Z.; Wang, K.; Zhu, Z.J.; Song, H.T.; Xia, X.H. One-step Immobilization of Glucose Oxidase in a Silica Matrix on a Pt Electrode by an Electrochemically Induced Sol-Gel Process. Langmuir 2007, 23, 11896–11900. [Google Scholar]
  195. Tsai, Y.C.; Li, S.C.; Chen, J.M. Cast Thin Film Biosensor Design Based on a Nafion Backbone, A Multiwalled Carbon Nanotube Conduit, and a Glucose Oxidase Function. Langmuir 2005, 21, 3653–3658. [Google Scholar]
  196. Klimova, T.; Rojas, M. L.; Castillo, P.; Cuevas, R.; Ramirez, J. Characterization of Al2O3-ZrO2 Mixed Oxide Catalytic Supports Prepared by the Sol-Gel Method. Microporous Mesoporous Mat 1998, 20, 293–306. [Google Scholar]
  197. He, C.; Liu, J.; Xie, L.; Zhang, Q.; Li, C.; Gui, D.; Zhang, G.; Wu, C. Activity and Thermal Stability Improvements of Glucose Oxidase upon Adsorption on Core-Shell PMMA-BSA Nanoparticles. Langmuir 2009, 25, 13456–13460. [Google Scholar]
  198. Liu, B.; Cao, Y.; Chen, D.; Kong, J.; Deng, J. Amperometric Biosensor Based on a Nanoporous ZrO2 matrix. Anal. Chim. Acta 2003, 478, 59–66. [Google Scholar]
  199. Zong, S.; Cao, Y.; Zhou, Y.; Ju, H. Zirconia Nanoparticles Enhanced Grafted Collagen Tri-Helix Scaffold for Unmediated Biosensing of Hydrogen Peroxide. Langmuir 2006, 22, 8915–8919. [Google Scholar]
  200. Yang, X.; Chen, X.; Yang, L.; Yang, W. Direct Electrochemistry and Electrocatalysis of Horseradish Peroxidase in α-Zirconium Phosphate Nanosheet Film. Bioelectrochemistry 2008, 74, 90–95. [Google Scholar]
  201. Kim, H-J.; Yoon, S.H.; Choi, H.N.; Lyu, Y.K.; Lee, W.-Y. Amperometric Glucose Biosensor Based on Sol-Gel-Derived Zirconia/Nafion Composite Film as Encapsulation Matrix. Bull. Korean Chem. Soc 2006, 27, 65–70. [Google Scholar]
  202. Yang, X.; Zhang, Q.; Sun, Y.; Liu, S. Direct Electron Transfer Reactivity of Glucose Oxidase on Electrodes Modified With Zirconium Dioxide Nanoparticles. IEEE Sens. J 2007, 7, 1735–1740. [Google Scholar]
  203. Li, C.; Liu, Y.; Li, L.; Du, Z.; Xu, S.; Zhang, M.; Yin, X.; Wang, T. A Novel Amperometric Biosensor Based on NiO Hollownanospheres for Biosensing Glucose. Talanta 2008, 77, 455–459. [Google Scholar]
  204. Park, J.Y.; Kim, Y.H.; Seong, A.; Yoo, Y.J. Amperometric Determination of Glucose Based on Direct Electron Transfer between Glucose Oxidase and Tinoxide. Biotechnol. Bioprocess Eng 2008, 13, 431–435. [Google Scholar]
  205. Umar, A.; Rahman, M.M.; Hahn, Y.-B. MgO Polyhedral Nanocages and Nanocrystals Based Glucose Biosensor. Electrochem Commun 2009, 11, 1353–1357. [Google Scholar]
  206. Irhayem, E.A.; Elzanowska, H.; Jhas, A.S.; Skrzynecka, B.; Birss, V. Glucose Detection Based on Electrochemically Formed Ir Oxide Films. J. Electroanal. Chem 2002, 538–539, 153–164. [Google Scholar]
  207. Zhang, X.; Chan, K.-Y.; Tseung, A.C.C. Electrochemical Oxidation of Glucose by Pt/WO3 Electrode. J. Electroanal. Chem 1995, 386, 24l–243. [Google Scholar]
  208. Cui, G.; Kim, S.J.; Choi, S.H.; Nam, H.; Cha, G.S. A Disposable Amperometric Sensor Screen Printed on a Nitrocellulose Strip: A Glucose Biosensor Employing Lead Oxide as an Interference-Removing Agent. Anal. Chem 2000, 72, 1925–1929. [Google Scholar]
  209. Kotzian, P.; Brázdilová, P.; Řezková, S.; Kalcher, K.; Vytřas, K. Amperometric Glucose Biosensor Based on Rhodium Dioxide-Modified Carbon Ink. Electroanalysis 2006, 18, 1499–1504. [Google Scholar]
  210. Wilson, M.S.; Rauh, R.D. Novel Amperometric Immunosensors Based on Iridium Oxide Matrices. Biosens. Bioelectron 2004, 19, 693–699. [Google Scholar]
  211. Glezer, V.; Lev, O. Sol-Gel Vanadium Pentaoxide Glucose Biosensor. J. Am. Chem. Soc 1993, 115, 2533–2534. [Google Scholar]
  212. Sÿljukić, B.; Banks, C.E.; Compton, R.G. Iron Oxide Particles Are the Active Sites for Hydrogen Peroxide Sensing at Multiwalled Carbon Nanotube Modified Electrodes. Nano Lett 2006, 6, 1556–1558. [Google Scholar]
  213. Kumar, A.S.; Chen, P.-Y.; Chien, S.-H.; Zen, J.-M. Development of an Enzymeless/Mediatorless Glucose Sensor Using Ruthenium Oxide-Prussian Blue Combinative Analogue. Electroanalysis 2005, 17, 210–222. [Google Scholar]
  214. Carnes, C.L.; Klabunde, K.J. The Catalytic Methanol Synthesis over Nanoparticle Metal Oxide Catalysts. J. Mol. Catal.A: Chem 2003, 194, 227–236. [Google Scholar]
  215. Biju, V.; Khadar, M.A. Analysis of AC Electrical Properties of Nanocrystalline Nickel Oxide. Mater. Sci. Eng. A 2001, 304–306, 814–817. [Google Scholar]
  216. Bain, S.-W.; Ma, Z.; Cui, Z.-M.; Zhang, l-S.; Niu, F.; Song, W.-G. Synthesis of Micrometer-Sized Nanostructured Magnesium Oxide and Its High Catalytic Activity in the Claisen-Schmidt Condensation Reaction. J. Phys. Chem. C 2008, 112, 11340–11344. [Google Scholar]
  217. Yu, J.C.; Xu, A.; Zhang, L.; Song, R.; Wu, L. Synthesis and Characterization of Porous Magnesium Hydroxide and Oxide Nanoplates. J. Phys. Chem. B 2004, 108, 64–70. [Google Scholar]
  218. Zhan, J.; Bando, Y.; Hu, J.; Golberg, D. Bulk Synthesis of Single-Crystalline Magnesium Oxide Nanotubes. Inorg. Chem 2004, 43, 2462–2464. [Google Scholar]
  219. Lu, L.; Zhang, L.; Zhang, X.; Wu, Z.; Huan, S.; Shen, G.; Yu, R. A MgO Nanoparticles Composite Matrix-Based Electrochemical Biosensor for Hydrogen Peroxide with High Sensitivity. Electroanalysis 2010, 22, 471–477. [Google Scholar]
  220. Kotzian, P.; Brázdilova, P.; Kalcher, K.; Vytřas, K. Determination of Hydrogen Peroxide, Glucose and Hypoxanthine using (Bio)Sensors Based on Ruthenium Dioxide-Modified Screen-Printed Electrodes. Anal. Lett 2005, 38, 1099–1113. [Google Scholar]
  221. Kaushik, A.; Khan, R.; Solanki, P.R.; Pandey, P.; Alam, J.; Ahmad, S.; Malhotra, B.D. Iron Oxide Nanoparticles–Chitosan Composite Based Glucose Biosensor. Biosens Bioelectron 2008, 24, 676–683. [Google Scholar]
  222. Qiu, J.; Peng, H.; Liang, R. Ferrocene-modified Fe3O4@SiO2 Magnetic Nanoparticles as Building Blocks for Construction of Reagentless Enzyme-Based Biosensors. Electrochem. Commun 2007, 9, 2734–2738. [Google Scholar]
  223. Poghossian, A.S. Method of Fabrication of ISFET-based Biosensors on an Si–SiO2–Si Structure. Sens. Actuat. B-Chem 1997, 44, 361–364. [Google Scholar]
  224. Kormos, F.; Sziráki, L.; Tarsiche, I. Potentiometric Biosensor for Urinary Glucose Level Monitoring. LRA 2000, 12, 291–295. [Google Scholar]
  225. Zhao, Z.; Lei, W.; Zhang, X.; Wang, B.; Jiang, H. ZnO-Based Amperometric Enzyme Biosensors. Sensors 2010, 10, 1216–1231. [Google Scholar]
  226. Teixeira, M.F.S.; Fatibello-Filho, O.; Ferracin, L.C.; Rocha-Filho, R.C.; Bocchi, N. A λ-MnO-Based Graphite–Epoxy Electrode as Lithium Ion Sensor. Sens. Actuat. B-Chem 2000, 67, 96–100. [Google Scholar]
  227. Pang, X.; He, D.; Luo, S.; Cai, Q. An Amperometric Glucose Biosensor Fabricated with Pt Nanoparticle-Decorated Carbon Nanotubes/TiO2 Nanotube Arrays Composite. Sens. Actuat. B-Chem 2009, 137, 134–138. [Google Scholar]
  228. Nakatou, M.; Miura, N. Detection of Propene by Using New-Type Impedancemetric Zirconiabased Sensor Attached with Oxide Sensing-Electrode. Sens. Actuat. B-Chem. 2006, 120, 57–62. [Google Scholar]
Figure 1. Schematic illustration of the configuration of the MOSFET-based potentiometric glucose detection using an extended-gate functionalized-ZnO nanowire as a working electrode and the Ag/AgCl reference electrode (reproduced with permission from [54]. Copyright 2009, IEEE).
Figure 1. Schematic illustration of the configuration of the MOSFET-based potentiometric glucose detection using an extended-gate functionalized-ZnO nanowire as a working electrode and the Ag/AgCl reference electrode (reproduced with permission from [54]. Copyright 2009, IEEE).
Sensors 10 04855f1
Figure 2. (A) A schematic illustration of the first generation and (B) the second generation amperometric glucose sensors (redrawn from reference [61]).
Figure 2. (A) A schematic illustration of the first generation and (B) the second generation amperometric glucose sensors (redrawn from reference [61]).
Sensors 10 04855f2
Figure 3. Schematic illustration of the preparation of the third generation amperometric glucose sensor based on the GOx-immobilized aligned ZnO nanorod (redrawn from reference [69]).
Figure 3. Schematic illustration of the preparation of the third generation amperometric glucose sensor based on the GOx-immobilized aligned ZnO nanorod (redrawn from reference [69]).
Sensors 10 04855f3
Figure 4. (a) Scanning electron microscope (SEM) image of the ZnO nanotube arrays; the energy dispersive X-ray spectroscopy (EDS) analysis (inset). (b) SEM image of the surface modified ZnO nanotube arrays; the EDS analysis (inset). (c) Typical amperometric response curve of GOx/ZnO nanotube arrays/ITO electrodes with the glucose concentration increases in 10 μM per step by successive addition of glucose to the 0.02 M phosphate buffer solution (PBS) at pH 7.4 under stirring. The applied potential was +0.8 V vs. SCE (reproduced with permission from [83]. Copyright 2009, The American Chemical Society).
Figure 4. (a) Scanning electron microscope (SEM) image of the ZnO nanotube arrays; the energy dispersive X-ray spectroscopy (EDS) analysis (inset). (b) SEM image of the surface modified ZnO nanotube arrays; the EDS analysis (inset). (c) Typical amperometric response curve of GOx/ZnO nanotube arrays/ITO electrodes with the glucose concentration increases in 10 μM per step by successive addition of glucose to the 0.02 M phosphate buffer solution (PBS) at pH 7.4 under stirring. The applied potential was +0.8 V vs. SCE (reproduced with permission from [83]. Copyright 2009, The American Chemical Society).
Sensors 10 04855f4
Figure 5. Reaction mechanism of glucose at a MnO2/GOx modified SPE based on heterogeneous carbon material: (i) enzymatic oxidation of glucose by GOx, (ii) chemical oxidation of H2O2, and (iii) chemical reduction of H2O2 (redrawn from reference [133]).
Figure 5. Reaction mechanism of glucose at a MnO2/GOx modified SPE based on heterogeneous carbon material: (i) enzymatic oxidation of glucose by GOx, (ii) chemical oxidation of H2O2, and (iii) chemical reduction of H2O2 (redrawn from reference [133]).
Sensors 10 04855f5
Figure 6. Schematic illustration of two possible biochemical reaction mechanisms on the GOx/CeO2/Pt electrode (redrawn from reference [176]).
Figure 6. Schematic illustration of two possible biochemical reaction mechanisms on the GOx/CeO2/Pt electrode (redrawn from reference [176]).
Sensors 10 04855f6
Table 1. Metal-oxides and metal-oxide composites available for glucose sensors and their functional properties.
Table 1. Metal-oxides and metal-oxide composites available for glucose sensors and their functional properties.
Electrode matrixDetection techniquesEnzymatic/nonenzymaticSensitivity/detection limit (μM)Response time(s)/applied potential(V)Ref.

CuO nanospheresAmperometricnonenzymatic404.53 μA mM−1 cm−2/1−/+0.60[12]
MOSFET using a ZnO nanowiresPotentiometricenzymatic−/∼10−3[54]
n-type silicon substrates covered with SiO2 and/or Al2O3Potentiometricenzymatic13 mV mM−1/−[56]
ENFET doped with SiO2 nanoparticlesPotentiometricenzymatic48 mV pH−1 in the pH range of 2–12/25300/−[57]
ZnO nanowireAmperometricenzymatic26.3 mA mA−1 cm−2/0.710/+0.8[68]
ZnO nanorodsAmperometricenzymatic−/3<5/−0.1[69]
Nano-basket SnO2 templated in porous Al2O3Conductmetricenzymatic−/in the range of 5 × 103–2 × 104[82]
ZnO nanotubeAmperometricenzymaitc30.85 μA mM−1 cm−2/10<6/+0.8[83]
ZnO nanorodAmperometricenzymatic23.1 μA mM−1 cm−2/10<5/+0.8[88]
ZnO:Co nanoclusterAmperometricenzymatic13.3 μA mM−1 cm−2/208/0.55[91]
pyramid-shaped porous ZnOAmperometricenzymatic−/10−/−0.50[92]
ZnO nanotubeAmperometricenzymatic21.7 μA mM−1 cm−2/13/+0.8[93]
ZnO nanocombAmperometricenzymatic15.33 μA mM−1 cm−2/20<10/+0.8[94]
C-decorated ZnO nanowireAmperometricenzymatic237.8 μA mM−1 cm−2/0.2∼5/−0.45[95]
MWNTs/ZnO nanoparticleAmperometricenzymatic50.2mA cm−2 M−1/0.256/−0.1[100]
Pd (IV)-doped CuO oxide nanofiberAmperometricnonenzymatic1061.4 μA mM−1 cm−2/1.9 × 10−21/+0.3[113]
CuO nanofibreAmperometricnonenzymaic431.3 μA mM−1 cm−2/−∼1/+0.4[115]
CuO nanowireAmperometricnonenzymatic0.49 μA μmol−1 dm−3/0.049−/+0.33[116]
Cu2O/MWCNTs nanocompositesAmperometricnonenzymatic6.53 μA μmol−1 L−1/0.05−/−0.2[118]
MWNTs/CuO nanoparticleAmperometricnonenzymatic2596 μA mM−1 cm−2/0.2∼1/+0.4[119]
flower-shaped CuOAmperometricenzymatic47.19 μA mM−1 cm−2/1.37<5/+0.58[119]
MnO2/MWNTs nanocompositeAmperometricnonenzymatic33.19 μA mM−1/28 × 103−/+0.3[136]
TiO2 nanofilmAmperometricenzymatic−/∼1few second/−0.45[156]
Nanostructured TiO2/CNTAmperometricenzymatic0.3 μA mmol−1/−<10/−0.45[155]
Array-based TiO2Opticalenzymatic−/3.1–7.8[164]
Nanostructured CeO2Amperometricenzymatic0.00287 μA mg−1 dL−1 cm−2/12.0[179]
SiO2–Carbon NanocompositeAmperometricenzymatic−/34−/−0.4[186]
Nano-SiO2 and “unprotected” Pt nanoclustersAmperometricenzymatic3.85 μA mM−1/1.5−/+0.6[187]
TiO2/SiO2 nanocompositePhosphorescenceenzymatic−/1.2 × 10−4[188]
CNT/perfluorosulfonate ionomer–SiO2 nanocompositeAmperometricenzymatic5.01 μA mM−1/0.1∼6/+0.2[192]
ZrO2 nanoparticleAmperometricenzymatic−/+0.4[202]
NiO hollow nanospheresAmperometricenzymatic3.43μA Mm−1/47∼8/+0.35[203]
MgO polyhedral nanocages and nanocrystalsAmperometricenzymatic31.6 μA μM−1 cm−2/6.83 × 10−2 ± 0.02<5/+0.58[205]
Nitrocellulose, NC/PbO2Amperometricenzymatic0.183 μA mM−1 / −−/+0.7[208]
RhO2 modified carbon InkAmperometricenzymatic64 μA mM−1 cm−2/1.1128/−0.2[209]
RuOx –prussian blueAmperometricnonenzymatic6.2 μA mM−1 cm−2/40[213]
RuO2 modified Screen printed electrodeAmperometricenzymatic−/0.611−/+0.5[220]
Fe3O4 nanoparticle/ChitosanAmperometricenzymatic9.3 μA mM−1 cm−2/500∼5/−[221]
Ferrocene-modified Fe3O4@SiO2 magnetic nanoparticlesAmperometricenzymatic−/3.2−/+0.35[222]
Si–SiO2–SiPotentiometricenzymatic12 mV decade−1 in human urine/−90[223]
SnO2 filmPotentiometricenzymatic50 ± 2 ΔmV ΔpC−1/−∼300[224]
Table 2. Characteristics of most frequently-used metal oxides in prospective biosensors.
Table 2. Characteristics of most frequently-used metal oxides in prospective biosensors.
Metal-oxidesIEPAvailability of enzymatic/nonenzymatic sensorCompatibility with CNTCompatibility with conducting polymer, metal nanoparticleApplication for other biosensorsReference
ZnO9.5available/ N/AavailableN/A, CoH2O2, gas, cholesterol[84,88,91,100,225]
CuO6.5available/availableavailableN/A, Pd(IV)H2O2, carbohydrates, gas[112,113,118,119]
MnO24–5available/availableavailableavailable, N/Aascorbic acid, H2O2, Li+[133,134,135,226]
TiO23.9–8.2available/N/Aavailableavailable, PtH2O2, DNA hybridization, gas[137,157,227]
CeO2∼9available/ N/AN/AN/ADNA hybridization, H2O2[167,170172,176]
SiO21.7–3.5available/N/AavailableN/AH2O2, biomolecules, urea, penicillin[56,186,187,191]
ZrO24.15available/ N/AN/AN/AH2O2, gas[196,200,228]
*N/A= Not available

Share and Cite

MDPI and ACS Style

Rahman, M.M.; Ahammad, A.J.S.; Jin, J.-H.; Ahn, S.J.; Lee, J.-J. A Comprehensive Review of Glucose Biosensors Based on Nanostructured Metal-Oxides. Sensors 2010, 10, 4855-4886.

AMA Style

Rahman MM, Ahammad AJS, Jin J-H, Ahn SJ, Lee J-J. A Comprehensive Review of Glucose Biosensors Based on Nanostructured Metal-Oxides. Sensors. 2010; 10(5):4855-4886.

Chicago/Turabian Style

Rahman, Md. Mahbubur, A. J. Saleh Ahammad, Joon-Hyung Jin, Sang Jung Ahn, and Jae-Joon Lee. 2010. "A Comprehensive Review of Glucose Biosensors Based on Nanostructured Metal-Oxides" Sensors 10, no. 5: 4855-4886.

Article Metrics

Back to TopTop